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Related Concept Videos

Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
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Sequence determinants of human gene regulatory elements.

Biswajyoti Sahu1,2, Tuomo Hartonen1, Päivi Pihlajamaa1

  • 1Applied Tumor Genomics Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Nature Genetics
|February 22, 2022
PubMed
Summary
This summary is machine-generated.

This study reveals how DNA sequences control gene expression using machine learning and massively parallel reporter assays. Transcription factors primarily act additively, with enhancers influencing gene activity through diverse mechanisms.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Understanding gene expression regulation is crucial for deciphering biological processes.
  • The complete set of DNA sequence determinants controlling gene expression remains largely unknown.

Purpose of the Study:

  • To identify and characterize DNA sequence elements that regulate gene expression.
  • To explore the mechanisms by which transcription factors and enhancers control gene activity.

Main Methods:

  • Utilized massively parallel reporter assays (MPRAs) to test the transcriptional activity of a vast DNA sequence space.
  • Employed machine learning models to analyze the relationship between DNA sequences and gene expression levels.

Main Results:

  • Discovered that transcription factors (TFs) generally function additively with minimal complex grammar.
  • Identified three distinct types of enhancers: classical, closed chromatin, and chromatin-dependent.
  • Showed that most TFs exhibit similar activity across different cell types, with individual TFs capable of multiple regulatory functions.

Conclusions:

  • The TF binding motif is proposed as the fundamental unit of gene expression regulation.
  • Gene expression is controlled by a combination of additive TF actions and diverse enhancer mechanisms.