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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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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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Histone Modification02:32

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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Co-activators and Co-repressors02:04

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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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RNA Polymerase II Accessory Proteins02:36

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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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Spreading of Chromatin Modifications02:25

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
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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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Related Experiment Video

Updated: Aug 5, 2025

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
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Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark

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Histone modifications regulate pioneer transcription factor binding and cooperativity.

Kalyan Sinha1, Silvija Bilokapic1, Yongming Du1

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.

Biorxiv : the Preprint Server for Biology
|March 30, 2023
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Summary
This summary is machine-generated.

Pioneer transcription factors like Oct4 remodel chromatin, enabling cooperative binding with Sox2 for cell reprogramming. Epigenetic modifications on histones regulate this crucial Oct4 activity.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Structural Biology

Background:

  • Pioneer transcription factors (PTFs) like Oct4 and Sox2 are crucial for pluripotency and reprogramming.
  • Understanding how PTFs access compacted chromatin and cooperate remains a challenge.

Approach:

  • Utilized cryo-electron microscopy (cryo-EM) to determine structures of human Oct4 bound to nucleosomes.
  • Integrated structural data with biochemical assays to investigate Oct4-nucleosome interactions.

Key Points:

  • Oct4 binding alters nucleosome structure, repositioning DNA to facilitate cooperative binding of Oct4 and Sox2.
  • Oct4's activation domain interacts with histone H4 tails, promoting chromatin decompaction.
  • Oct4's DNA binding domain interacts with histone H3 tails; H3K27 modifications influence DNA positioning and factor cooperativity.

Conclusions:

  • The epigenetic landscape dynamically regulates Oct4 activity.
  • This regulation is essential for precise control of cell reprogramming processes.