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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 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.
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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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A Method to Study de novo Formation of Chromatin Domains
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Polycomb protein RYBP facilitates super-enhancer activity.

Yu Hong1, Ranran Dai2, Xinlan Li1,3

  • 1Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Molecular Medicine (Cambridge, Mass.)
|November 28, 2024
PubMed
Summary
This summary is machine-generated.

Polycomb protein RYBP activates gene transcription by interacting with Trithorax group proteins at super-enhancers. RYBP dysfunction is linked to diseases, revealing new roles for Polycomb proteins.

Keywords:
EnhancerEpigeneticHistone modificationPolycomb complexStem cell

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Area of Science:

  • Epigenetics and Gene Regulation
  • Developmental Biology

Background:

  • Polycomb proteins are traditionally known as transcriptional repressors.
  • Emerging evidence suggests Polycomb proteins also play roles in transcriptional activation.
  • The mechanisms underlying Polycomb-mediated transcriptional activation require further elucidation.

Purpose of the Study:

  • To investigate the role of Polycomb protein RYBP in transcriptional activation.
  • To explore the mechanism by which RYBP regulates gene expression at super-enhancers.

Main Methods:

  • Analysis of ChIP-seq, RNA-seq, and HiChIP data from embryonic stem cells, epidermal progenitor cells, and mesodermal cells.
  • RYBP depletion experiments were performed in vitro and in vivo.

Main Results:

  • RYBP localizes to super-enhancers (SEs) in embryonic stem cells, distinct from core Polycomb group components.
  • RYBP depletion impairs H3K27ac deposition, reduces SE-associated gene expression, and decreases enhancer RNA (seRNA) transcription.
  • RYBP cooperates with Trithorax group component WDR5 at SEs, influencing seRNA expression and H3K4me3 deposition.

Conclusions:

  • RYBP collaborates with Trithorax group proteins to regulate super-enhancer activity.
  • RYBP dysfunction is implicated in various diseases, including cancers and developmental disorders.
  • These findings offer novel insights into the transcriptionally active functions of Polycomb proteins in cell fate determination.