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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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Cooperative Binding of Transcription Regulators02:13

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Master Transcription Regulators02:23

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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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Regulation of Expression Occurs at Multiple Steps02:24

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Deciphering the multi-scale, quantitative cis-regulatory code.

Seungsoo Kim1, Joanna Wysocka1

  • 1Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Molecular Cell
|January 24, 2023
PubMed
Summary
This summary is machine-generated.

Understanding gene transcription regulation is key. This involves transcription factors, cofactors, and DNA sequences, all interacting within chromatin and nuclear organization to control gene expression.

Keywords:
RNA polymerase IIactivation domainchromatincis-regulatory codecis-regulatory elementcoactivatorcofactorcorepressorenhancergene regulationinsulatornucleosomepioneer factorpromoterregulatory domainrepression domainsilencertopologically associating domaintranscriptiontranscription factor

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Area of Science:

  • Molecular Biology
  • Genomics
  • Systems Biology

Background:

  • Gene transcription regulation is fundamental to cellular function and organism development.
  • The cis-regulatory code dictates gene expression levels and timing, but remains incompletely understood.

Purpose of the Study:

  • To discuss the major regulatory layers influencing transcriptional outputs.
  • To highlight the interplay of DNA sequence, cellular context, and regulatory elements.
  • To propose a framework for cracking the cis-regulatory code.

Main Methods:

  • Review and synthesis of current knowledge on transcription factor binding and cofactor function.
  • Analysis of cis-regulatory elements (enhancers, silencers, promoters) and their modular activities.
  • Discussion of the integration of regulatory landscapes, chromatin states, and nuclear organization.

Main Results:

  • Transcription factors bind DNA in a dosage-dependent and cooperative manner.
  • Cofactors modulate transcription factor activity and cis-regulatory element function.
  • Complex interplay exists between regulatory elements, chromatin, and nuclear organization.

Conclusions:

  • A comprehensive understanding requires integrating multiple regulatory layers.
  • A mechanistically informed, quantitative model is proposed as the key to deciphering the cis-regulatory code.
  • Further research integrating diverse regulatory mechanisms is essential for advancing gene regulation studies.