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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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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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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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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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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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Overview
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Related Experiment Video

Updated: Aug 8, 2025

In Vitro Selection of Engineered Transcriptional Repressors for Targeted Epigenetic Silencing
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Gene silencing dynamics are modulated by transiently active regulatory elements.

Marit W Vermunt1, Jing Luan2, Zhe Zhang3

  • 1Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.

Molecular Cell
|March 3, 2023
PubMed
Summary

Transcription factor GATA1 silences the Kit gene during red blood cell development. A transient regulatory element delays silencing, which is eventually removed by the FOG1/NuRD complex.

Keywords:
FOG1/NuRD complexGATA1erythroid differentiationgene silencingtranscriptional regulationtransient enhancer

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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Transcriptional enhancers are well-studied, but cis-regulatory elements mediating gene repression are less understood.
  • The transcription factor GATA1 plays a dual role in erythroid differentiation, activating and repressing specific genes.
  • The precise mechanisms of GATA1-mediated gene silencing, particularly for proliferative genes like Kit, require further investigation.

Purpose of the Study:

  • To elucidate the mechanism by which GATA1 represses the proliferative gene Kit during murine erythroid cell maturation.
  • To characterize the dynamic regulatory events, including enhancer inactivation and the formation of intronic regulatory regions, involved in Kit gene silencing.
  • To investigate the role of the FOG1/NuRD complex in the ultimate erasure of transient regulatory elements during gene repression.

Main Methods:

  • Analysis of gene silencing stages from initial loss of activation to heterochromatinization.
  • Identification and characterization of a transient intronic regulatory region marked by H3K27ac, short noncoding RNAs, and de novo chromatin looping.
  • Investigation using a disease-associated GATA1 variant to study the FOG1/NuRD complex's role in element erasure.
  • Genome-wide analyses across different cell types and species to identify similar transiently active elements.

Main Results:

  • GATA1 inactivates an upstream enhancer of the Kit gene.
  • A novel intronic regulatory region, marked by H3K27ac and noncoding RNAs, transiently forms and delays Kit silencing.
  • The FOG1/NuRD deacetylase complex is essential for the erasure of this transient intronic element.
  • Genome-wide studies reveal that transiently active elements are common at genes undergoing repression across various contexts.

Conclusions:

  • Regulatory elements can possess self-limiting properties through dynamic co-factor utilization.
  • The kinetics of gene silencing are modulated by transient regulatory elements, a widespread phenomenon.
  • Understanding these dynamic regulatory mechanisms is crucial for comprehending erythroid differentiation and gene regulation.