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7.5B: The Promoter and the Transcription Machinery - Biology

7.5B: The Promoter and the Transcription Machinery - Biology


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Learning Objectives

  • Describe the role of promoters in RNA transcription

Genes are organized to make the control of gene expression easier. The promoter region is immediately upstream of the coding sequence. This region can be short (only a few nucleotides in length) or quite long (hundreds of nucleotides long). The longer the promoter, the more available space for proteins to bind. This also adds more control to the transcription process. The length of the promoter is gene-specific and can differ dramatically between genes. Consequently, the level of control of gene expression can also differ quite dramatically between genes. The purpose of the promoter is to bind transcription factors that control the initiation of transcription.

Within the promoter region, just upstream of the transcriptional start site, resides the TATA box. This box is simply a repeat of thymine and adenine dinucleotides (literally, TATA repeats). RNA polymerase binds to the transcription initiation complex, allowing transcription to occur. To initiate transcription, a transcription factor (TFIID) is the first to bind to the TATA box. Binding of TFIID recruits other transcription factors, including TFIIB, TFIIE, TFIIF, and TFIIH to the TATA box. Once this transcription initiation complex is assembled, RNA polymerase can bind to its upstream sequence. When bound along with the transcription factors, RNA polymerase is phosphorylated. This releases part of the protein from the DNA to activate the transcription initiation complex and places RNA polymerase in the correct orientation to begin transcription; DNA-bending protein brings the enhancer, which can be quite a distance from the gene, in contact with transcription factors and mediator proteins.

In addition to the general transcription factors, other transcription factors can bind to the promoter to regulate gene transcription. These transcription factors bind to the promoters of a specific set of genes. They are not general transcription factors that bind to every promoter complex, but are recruited to a specific sequence on the promoter of a specific gene. There are hundreds of transcription factors in a cell that each bind specifically to a particular DNA sequence motif. When transcription factors bind to the promoter just upstream of the encoded gene, they are referred to as cis-acting elements because they are on the same chromosome, just next to the gene. The region that a particular transcription factor binds to is called the transcription factor binding site. Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.

Key Points

  • The purpose of the promoter is to bind transcription factors that control the initiation of transcription.
  • The promoter region can be short or quite long; the longer the promoter is, the more available space for proteins to bind.
  • To initiate transcription, a transcription factor (TFIID) binds to the TATA box, which causes other transcription factors to subsequently bind to the TATA box.
  • Once the transcription initiation complex is assembled, RNA polymerase can bind to its upstream sequence and is then phosphorylated.
  • Phosphorylation of RNA polymerase releases part of the protein from the DNA to activate the transcription initiation complex and places RNA polymerase in the correct orientation to begin transcription.
  • Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.

7.00x Introduction to Biology or similar (undergraduate biochemistry, molecular biology, and genetics) and 7.28.1x Molecular Biology or similar (advanced DNA replication and repair)

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About this course

In Part 2 of this Molecular Biology course, you’ll explore transcription of DNA to RNA, a key part of the central dogma of biology and the first step of gene expression.

Did you know that transposable elements, the genetic information that can move from location to location, make up roughly 50 % of the human genome? Did you know that scientists have linked their movement into specific genes to the causes of certain diseases? You’ll also learn how these “jumping genes” work and how scientists study them in Molecular Biology: Transcription and Transposition.

Are you ready to go beyond the “what" of scientific information presented in textbooks and explore how scientists deduce the details of these molecular models?

Take a behind-the-scenes look at modern molecular genetics, from the classic experimental events that identified the proteins and elements involved in transcription and transposition to cutting-edge assays that apply the power of genome sequencing. We've designed the problems in this course to build your experimental design and data analysis skills.

Let’s explore the limits of our current knowledge about the transcription machinery and mechanisms of transposition. If you are up for the challenge, join us in 7.28.2x Molecular Biology: Transcription and Transposition.

What you'll learn

  • How to compare and contrast transcription in prokaryotes and eukaryotes
  • How to describe several mechanisms of transposition
  • How to analyze protein structures to infer functional information
  • How todesign the best experiment to test a hypothesis
  • How to interpret data from transcription and transposition experiments

Syllabus

Week 1 : Machinery and Promoters of Bacterial Transcription

Week 2 : Bacterial Regulation of Bacterial Transcription

Week 3 : Machinery and Promoters of Eukaryotic Transcription


Biology 171

By the end of this section, you will be able to do the following:

  • Discuss the role of transcription factors in gene regulation
  • Explain how enhancers and repressors regulate gene expression

Like prokaryotic cells, the transcription of genes in eukaryotes requires the action of an RNA polymerase to bind to a DNA sequence upstream of a gene in order to initiate transcription. However, unlike prokaryotic cells, the eukaryotic RNA polymerase requires other proteins, or transcription factors, to facilitate transcription initiation. RNA polymerase by itself cannot initiate transcription in eukaryotic cells. There are two types of transcription factors that regulate eukaryotic transcription: General (or basal) transcription factors bind to the core promoter region to assist with the binding of RNA polymerase. Specific transcription factors bind to various regions outside of the core promoter region and interact with the proteins at the core promoter to enhance or repress the activity of the polymerase.

View the process of Transcription (video)—the making of RNA from a DNA template.

The Promoter and the Transcription Machinery

Genes are organized to make the control of gene expression easier. The promoter region is immediately upstream of the coding sequence. This region can be short (only a few nucleotides in length) or quite long (hundreds of nucleotides long). The longer the promoter, the more available space for proteins to bind. This also adds more control to the transcription process. The length of the promoter is gene-specific and can differ dramatically between genes. Consequently, the level of control of gene expression can also differ quite dramatically between genes. The purpose of the promoter is to bind transcription factors that control the initiation of transcription.

Within the core promoter region, 25 to 35 bases upstream of the transcriptional start site, resides the TATA box. The TATA box has the consensus sequence of 5’-TATAAA-3’. The TATA box is the binding site for a protein complex called TFIID, which contains a TATA-binding protein. Binding of TFIID recruits other transcription factors, including TFIIB, TFIIE, TFIIF, and TFIIH. Some of these transcription factors help to bind the RNA polymerase to the promoter, and others help to activate the transcription initiation complex.

In addition to the TATA box, other binding sites are found in some promoters. Some biologists prefer to restrict the range of the eukaryotic promoter to the core promoter, or polymerase binding site, and refer to these additional sites as promoter-proximal elements, because they are usually found within a few hundred base pairs upstream of the transcriptional start site. Examples of these elements are the CAAT box, with the consensus sequence 5’-CCAAT-3’ and the GC box, with the consensus sequence 5’-GGGCGG-3’. Specific transcription factors can bind to these promoter-proximal elements to regulate gene transcription. A given gene may have its own combination of these specific transcription-factor binding sites. There are hundreds of transcription factors in a cell, each of which binds specifically to a particular DNA sequence motif. When transcription factors bind to the promoter just upstream of the encoded gene, it is referred to as a cis-acting element , because it is on the same chromosome just next to the gene. Transcription factors respond to environmental stimuli that cause the proteins to find their binding sites and initiate transcription of the gene that is needed.

Enhancers and Transcription

In some eukaryotic genes, there are additional regions that help increase or enhance transcription. These regions, called enhancers , are not necessarily close to the genes they enhance. They can be located upstream of a gene, within the coding region of the gene, downstream of a gene, or may be thousands of nucleotides away.

Enhancer regions are binding sequences, or sites, for specific transcription factors. When a protein transcription factor binds to its enhancer sequence, the shape of the protein changes, allowing it to interact with proteins at the promotor site. However, since the enhancer region may be distant from the promoter, the DNA must bend to allow the proteins at the two sites to come into contact. DNA bending proteins help to bend the DNA and bring the enhancer and promoter regions together ((Figure)). This shape change allows for the interaction of the specific activator proteins bound to the enhancers with the general transcription factors bound to the promoter region and the RNA polymerase.


Turning Genes Off: Transcriptional Repressors

Like prokaryotic cells, eukaryotic cells also have mechanisms to prevent transcription. Transcriptional repressors can bind to promoter or enhancer regions and block transcription. Like the transcriptional activators, repressors respond to external stimuli to prevent the binding of activating transcription factors.

Section Summary

To start transcription, general transcription factors, such as TFIID, TFIIB, and others, must first bind to the TATA box and recruit RNA polymerase to that location. Additional transcription factors may also bind to other regulatory elements at the promoter to increase or prevent transcription. In addition to promoter sequences, enhancer regions help augment transcription. Enhancers can be upstream, downstream, within a gene itself, or on other chromosomes. Specific transcription factors bound to enhancer regions may either increase or prevent transcription.

Free Response

A mutation within the promoter region can alter transcription of a gene. Describe how this can happen.

A mutation in the promoter region can change the binding site for a transcription factor that normally binds to increase transcription. The mutation could either decrease the ability of the transcription factor to bind, thereby decreasing transcription, or it can increase the ability of the transcription factor to bind, thus increasing transcription.

What could happen if a cell had too much of an activating transcription factor present?

If too much of an activating transcription factor were present, then transcription would be increased in the cell. This could lead to dramatic alterations in cell function.

A scientist identifies a potential transcription regulation site 300bp downstream of a gene and hypothesizes that it is a repressor. What experiment (with results) could he perform to support this hypothesis?

The easiest way to test his hypothesis would be to mutate the site in a cell, and monitor levels of the mRNA transcript made from the gene. If the levels of transcript increase in the mutated cell, then the site was repressing transcription.

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Practicing Dna Transcription And Translation Answer Key / DNA Transcription and Translation Practice Worksheet with .

Practicing Dna Transcription And Translation Answer Key

Article aug 21, 2019 | by molly campbell, science writer, technology networks. Stop codon — uaa, uag or uga. Transcription is the process by which dna is copied (transcribed) to mrna, which carries the information needed for protein synthesis. What would be the corresponding sequence to the following dna sequence as a result of transcription? In most cases, promoters exist.

Nonsense mutation — change in dna sequence in which a codon for an amino acid is changed into a stop codon. Transcription is the name given to the process in which dna is copied to make a complementary strand of rna. Transcription is the process by which dna is copied (transcribed) to mrna, which carries the information needed for protein synthesis. It con tains thy mine instead of uracil.rnaproteinsynthesisse key qn85p6yq02n1see all results for this questionfeedback unit 6. In most cases, promoters exist. A c c c c t c t. Transcription — making a complementary mrna molecule from the dna. In the first trial, the phages contained radioactive dna, and radioactivity was detected in the bacteria. Organisms are made up of proteins that are, in turn, made up of amino acids. Dna vs rna to understand fully the different processes involved in gene expression, it is key that you can know the differences between dna and rna.

Transcription and Translation Worksheet Answer Key from briefencounters.ca Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro. Images, music, & animations do not belong to me. Transcription and translation practice worksheet example: Genetic practice problems for you to try! Transcription, translation and replication from the perspective of dna and rna #2 a c t dna: › transcribing and translating dna practice › transcription and translation practice key practicing dna transcription and translation. How dna is copied (replication). Organisms are made up of proteins that are, in turn, made up of amino acids. Transcription is the name given to the process in which dna is copied to make a complementary strand of rna. This mrna then exits the nucleus, where it provides the basis for the translation of dna.

The intracellular level of a bacterial protein can a promoter is a dna sequence onto which the transcription machinery binds and initiates transcription.

Transcription, translation and replication from the perspective of dna and rna #2 a c t dna: Genetic practice problems for you to try! In most cases, promoters exist. Dna (deoxyribonucleic acid) is one of the most important molecules in your body, and though the short answer is a whole lot of twisting and winding. Dna vs rna to understand fully the different processes involved in gene expression, it is key that you can know the differences between dna and rna. Therefore, the processes of transcription, translation, and mrna degradation can all occur simultaneously. Transcription into rna, then to amino acids. By controlling the production of mrna in the nucleus. What would be the corresponding sequence to the following dna sequence as a result of transcription? Transcription and translation practice worksheet example: Dna carries information for the production of all proteins a image: Biology corner dna coloring transcription and… dna coloring transcription & translation. In the first trial, the phages contained radioactive dna, and radioactivity was detected in the bacteria. Rna then undergoes translation to make proteins.

Stop codon — uaa, uag or uga. 2.7 dna replication, transcription, translation. Biology corner dna coloring transcription and… dna coloring transcription & translation. Therefore, the processes of transcription, translation, and mrna degradation can all occur simultaneously. Genetic information in dna can be accurately copied and can be translated to make the translation is the process of protein synthesis in which the genetic information encoded in mrna is translated into a sequence of amino acids in a. Dna (deoxyribonucleic acid) is one of the most important molecules in your body, and though the short answer is a whole lot of twisting and winding. 1 2 3 4 5 6 dna transcription & translation worksheet. Transcription and translation practice worksheet example: Evolution (dna replication is not perfect).

16 Best Images of 13 1 RNA Worksheet Answer Key - Chapter . from www.worksheeto.com › transcribing and translating dna practice › transcription and translation practice key practicing dna transcription and translation. Evolution (dna replication is not perfect). #2 a c t dna: Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro. Dna vs rna to understand fully the different processes involved in gene expression, it is key that you can know the differences between dna and rna. Transcription is the process by which dna is copied (transcribed) to mrna, which carries the information needed for protein synthesis. Schematic representation of the two strands of dna during transcription and the resulting rna transcript. Transcription is the name given to the process in which dna is copied to make a complementary strand of rna.

Transcription and translation practice worksheet example:

Transcription, translation and replication from the perspective of dna and rna Therefore, the processes of transcription, translation, and mrna degradation can all occur simultaneously. Genetic information in dna can be accurately copied and can be translated to make the translation is the process of protein synthesis in which the genetic information encoded in mrna is translated into a sequence of amino acids in a. 2.7 dna replication, transcription, translation. The fat cat sat bac. Dna carries information for the production of all proteins a image: Dna replication, transcription, and translation. Images, music, & animations do not belong to me. Dna transcription and translation worksheet answer key from transcription and translation transcription and translation practice worksheets answer keys are designed to provide the answers to the questions. Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro. The two main steps in gene expression are transcription and translation.

The fat cat sat bac. Dna carries information for the production of all proteins a image: 1 2 3 4 5 6 dna transcription & translation worksheet.

16 Best Images of 13 1 RNA Worksheet Answer Key - Chapter . from www.worksheeto.com The two main steps in gene expression are transcription and translation. Stop codon — uaa, uag or uga. Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro. Transcription, translation and replication from the perspective of dna and rna In most cases, promoters exist. Article aug 21, 2019 | by molly campbell, science writer, technology networks. Dna wraps around protein clusters called before we discuss transcription and translation, the two processes key to protein synthesis, we need to. If the template side of a dna molecule is the sequence shown below, what will the coding side base sequence be? Termination of transcription is triggered when the rna polymerase encounters a particular dna sequence, causing the polymerase to lose affinity for the dna template. Evolution (dna replication is not perfect). Transcription and translation practice worksheet example: In an important experiment, bacteriophages were allowed to infect bacteria.

Transcription, translation and replication from the perspective of dna and rna

Organisms are made up of proteins that are, in turn, made up of amino acids. Make up your own example for a frameshift mutation. Another major difference is that, in prokaryotes, transcription and translation occur simultaneously while in eukaryotes, transcriptions must be complete before the translation mechanism is initiated. Nonsense mutation — change in dna sequence in which a codon for an amino acid is changed into a stop codon. How dna is copied (replication). In the first trial, the phages contained radioactive dna, and radioactivity was detected in the bacteria. The intracellular level of a bacterial protein can a promoter is a dna sequence onto which the transcription machinery binds and initiates transcription. Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro. Transcription is the name given to the process in which dna is copied to make a complementary strand of rna. Transcription, translation and replication from the perspective of dna and rna Dna wraps around protein clusters called before we discuss transcription and translation, the two processes key to protein synthesis, we need to. This mrna then exits the nucleus, where it provides the basis for the translation of dna. 2.7 dna replication, transcription, translation. Dna transcription definition, enzymes and function, dna transcription steps, and process.

Therefore, the processes of transcription, translation, and mrna degradation can all occur simultaneously.

Evolution (dna replication is not perfect).

Glencoe algebra 1 answer key for worksheets.

Images, music, & animations do not belong to me.

In most cases, promoters exist.

Termination of transcription is triggered when the rna polymerase encounters a particular dna sequence, causing the polymerase to lose affinity for the dna template.

By controlling the production of mrna in the nucleus.

In the first trial, the phages contained radioactive dna, and radioactivity was detected in the bacteria.

Dna transcription definition, enzymes and function, dna transcription steps, and process.

The two main steps in gene expression are transcription and translation.

By controlling the production of mrna in the nucleus.

In most cases, promoters exist.

421 775 просмотров 421 тыс.

The intracellular level of a bacterial protein can a promoter is a dna sequence onto which the transcription machinery binds and initiates transcription.

Dna wraps around protein clusters called before we discuss transcription and translation, the two processes key to protein synthesis, we need to.

Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro.

Schematic representation of the two strands of dna during transcription and the resulting rna transcript.

Make up your own example for a frameshift mutation.

It con tains thy mine instead of uracil.rnaproteinsynthesisse key qn85p6yq02n1see all results for this questionfeedback unit 6.

Transcription is the process by which dna is copied (transcribed) to mrna, which carries the information needed for protein synthesis.

Transcription is the first step of gene expression, where the messenger rna is decoded in a ribosome to produce polypeptide which later folds into an active pro.

A t g g g g a g a t t c a t g a translation protein (amino acid sequence):

2.7 dna replication, transcription, translation.

Transcription and translation practice worksheet example:

› transcribing and translating dna practice › transcription and translation practice key practicing dna transcription and translation.

421 775 просмотров 421 тыс.

In the first trial, the phages contained radioactive dna, and radioactivity was detected in the bacteria.

Therefore, the processes of transcription, translation, and mrna degradation can all occur simultaneously.

Transcription and translation practice worksheet answer key.

This mrna then exits the nucleus, where it provides the basis for the translation of dna.


7.5B: The Promoter and the Transcription Machinery - Biology

A promoter is a regulatory region of DNA located upstream (towards the 5' region) of of a gene, providing a control point for regulated gene transcription.

The promoter contains specific DNA sequences that are recognized by proteins known as transcription factors. These factors bind to the promoter sequences, recruiting RNA polymerase, the enzyme that synthesizes the RNA from the coding region of the gene.

1. Core promoter - the minimal portion of the promoter required to properly initiate transcription

  • Transcription Start Site (TSS)
  • Approximately -34
  • A binding site for RNA polymerase
  • General transcription factor binding sites

2. Proximal promoter - the proximal sequence upstream of the gene that tends to contain primary regulatory elements

Difference between Eukaryotic and Prokaryotic Promoters

Prokaryotic promoters

In prokaryotes, the promoter consists of two short sequences at -10 and -35 positions upstream from the transcription start site.

  • The sequence at -10 is called the Pribnow box, or the -10 element, and usually consists of the six nucleotides TATAAT. The Pribnow box is absolutely essential to start transcription in prokaryotes.
  • The other sequence at - 35 (the -35 element) usually consists of the six nucleotides TTGACA. Its presence allows a very high transcription rate.

Eukaryotic promoters

Eukaryotic promoters are extremely diverse and are difficult to characterize. They typically lie upstream of the gene and can have regulatory elements several kilobases away from the transcriptional start site. In eukaryotes, the transcriptional complex can cause the DNA to bend back on itself, which allows for placement of regulatory sequences far from the actual site of transcription. Many eukaryotic promoters, contain a TATA box (sequence TATAAA ), which in turn binds a TATA binding protein which assists in the formation of the RNA polymerase transcriptional complex. The TATA box typically lies very close to the transcriptional start site (often within 50 bases).


Telomere binding protein TRB1 is associated with promoters of translation machinery genes in vivo

Recently we characterised TRB1, a protein from a single-myb-histone family, as a structural and functional component of telomeres in Arabidopsis thaliana. TRB proteins, besides their ability to bind specifically to telomeric DNA using their N-terminally positioned myb-like domain of the same type as in human shelterin proteins TRF1 or TRF2, also possess a histone-like domain which is involved in protein–protein interactions e.g., with POT1b. Here we set out to investigate the genome-wide localization pattern of TRB1 to reveal its preferential sites of binding to chromatin in vivo and its potential functional roles in the genome-wide context. Our results demonstrate that TRB1 is preferentially associated with promoter regions of genes involved in ribosome biogenesis, in addition to its roles at telomeres. This preference coincides with the frequent occurrence of telobox motifs in the upstream regions of genes in this category, but it is not restricted to the presence of a telobox. We conclude that TRB1 shows a specific genome-wide distribution pattern which suggests its role in regulation of genes involved in biogenesis of the translational machinery, in addition to its preferential telomeric localization.

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Promoters

A promoter is a DNA sequence that can recruit transcriptional machinery and lead to transcription of the downstream DNA sequence. The specific sequence of the promoter determines the strength of the promoter (a strong promoter leads to a high rate of transcription initiation).

In addition to sequences that "promote" transcription, a promoter may include additional sequences known as operators that control the strength of the promoter. For example, a promoter may include a binding site for a protein that attracts or obstructs the RNAP binding to the promoter. The presence or absence of the protein will affect the strength of the promoter. Such a promoter is known as a regulated promoter.

An input/output description of promoter function

Sometimes, we ignore the details of how a promoter works and think of a promoter as a device that converts inputs into outputs. You can do this when designing a multi-component system that includes promoters whose activity must be regulated by other species in the system. A promoter can be thought of as a device that outputs a certain number of transcribing RNA polymerases per unit time. Promoters can have different numbers of inputs. A constitutive promoter has no inputs. Technically, even a constitutive promoter has inputs, such as the level of free RNA polymerase, but we often assume that levels of free RNA polymerase are either unchanging, or never be the limiting factor in transcription initiation. The level of a repressor that negatively regulates a promoter is an input to a promoter.


7.5B: The Promoter and the Transcription Machinery - Biology

a Biological Engineering Laboratory, Genetic Engineering Department, Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav), Campus Irapuato, Km. 9.6 Libramiento Norte Carr, Irapuato-León 36821, Irapuato Gto, Mexico
E-mail: [email protected]

Abstract

Genetic information in genomes is ordered, arranged in such a way that it constitutes a code, the so-called cis regulatory code. The regulatory machinery of the cell, termed trans-factors, decodes and expresses this information. In this way, genomes maintain a potential repertoire of genetic programs, parts of which are executed depending on the presence of active regulators in each condition. These genetic programs, executed by the regulatory machinery, have functional units in the genome delimited by punctuation-like marks. In genetic terms, these informational phrases correspond to transcription units, which are the minimal genetic information expressed consistently from initiation to termination marks. Between the start and final punctuation marks, additional marks are present that are read by the transcriptional and translational machineries. In this work, we look at all the experimentally described and predicted genetic elements in the bacterium Escherichia coli K-12 MG1655 and define a comprehensive architectural organization of transcription units to reveal the natural genome-design and to guide the construction of synthetic genetic programs.


Our goal is to uncover the molecular processes underlying the interplay between transcription and RNA processing to understand novel layers of gene regulation that will set the path for new therapeutic strategies to improve cancer treatments.

Exon type problem

Alternative RNA processing constitutes a major mechanism for diversifying the human transcriptome. Transcript isoform differences are predominantly driven by alternative first exons, skipped internal exons and alternative last exons. However, there is a lack of tools for classifying exons based on their isoform-specific usage from RNA-seq data. In collaboration with the Pai lab and the Burge lab, we built the FIHL (First-Internal-Hybrid-Last) exon pipeline that systematically classify exons depending on their isoform-specific usage. Using a combination of junction reads coverage and bayesian statistics, the FIHL index identified thousands of hybrid exons that were previously underestimated and uncovered the complexity of the human transcriptome.

Splicing determinants of transcription

We recently described a phenomenon affecting thousands of genes that we call exon-mediated activation of transcription starts (EMATS), in which the splicing of internal exons impacts promoter choice and the expression level of the gene. We observed that evolutionary gain of internal exons is associated with gain of new transcription start sites (TSS) nearby and increased gene expression. Inhibiting exon splicing reduced transcription from nearby promoters. Conversely, creation of new splice sites that enabled splicing of new exons activated transcription from cryptic promoters. The strongest effects occurred with weak promoters located proximal and upstream of efficiently spliced exons. Together, our findings support a model in which splicing recruits transcription machinery locally to influence TSS choice, and identify exon gain, loss and regulatory change as major contributors to the evolution of alternative promoters and gene expression in mammals.

Promoter determinants of splicing

How gene expression is orchestrated remains one of the most fundamental questions of molecular biology with implications for our understanding of cellular differentiation, development, disease, and evolution. The EMATS phenomenon shows that exons can feedback to promoters and previous literature suggests that changes in promoter structure can affect splice site selection in individual genes. However, how a DNA fragment which is not transcribed exerts such effects remains unknown. We called this phenomenon promoter-mediated activation of splicing (PMAS) and hypothesize that promoter features recruit sequence-specific binding factors that influence downstream alternative splicing decisions.