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HMGNs: The enhancer charmers.

Alexia Martínez de Paz1, Juan Ausió1

  • 1Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|December 29, 2015
PubMed
Summary

High-mobility group nucleosome-binding proteins (HMGNs) are crucial for establishing accessible chromatin domains at gene regulatory elements. These proteins fine-tune enhancer function by modulating nucleosome structure and histone modifications, impacting transcriptional initiation.

Keywords:
DNase I hypersensitive siteschromatinenhancers; high mobility group nucleosome-binding proteinstranscription

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Chromatin Biology

Background:

  • DNase I hypersensitive sites (DHSs) mark actively transcribed eukaryotic genes.
  • High-mobility group nucleosome-binding proteins (HMGNs), specifically HMGN1 and HMGN2, have long been implicated in creating these accessible chromatin domains.
  • Recent findings emphasize HMGNs' role at enhancers, suggesting a role in fine-tuning their structure and function.

Purpose of the Study:

  • To review the established and emerging roles of HMGNs in establishing and modulating chromatin accessibility.
  • To highlight the significance of HMGNs at enhancers for vertebrate gene regulation.
  • To explore the mechanisms by which HMGNs influence nucleosome structure and histone modifications.

Main Methods:

  • Literature review of studies on HMGN proteins, chromatin accessibility, and gene regulation.
  • Analysis of existing data on HMGN binding preferences and effects on nucleosome structure.
  • Examination of the interplay between HMGNs, histone H1, and histone modifications like H3S10ph.

Main Results:

  • HMGNs preferentially bind to nucleosomes, out-competing histone H1.
  • HMGNs can invade neighboring nucleosomes, altering chromatin structure.
  • HMGNs may modulate histone H3 at serine 10 (H3S10ph), a modification linked to enhancer function.

Conclusions:

  • HMGNs are key players in establishing and regulating the accessibility of transcriptional regulatory elements like promoters and enhancers.
  • Their ability to modify chromatin structure and histone marks contributes to the fine-tuning of enhancer activity and transcriptional initiation.
  • HMGNs are essential for vertebrate gene expression regulation through their impact on chromatin dynamics.