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In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
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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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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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Evolutionarily ancient BAH-PHD protein mediates Polycomb silencing.

Elizabeth T Wiles1, Kevin J McNaught1, Gurmeet Kaur2

  • 1Institute of Molecular Biology, University of Oregon, Eugene, OR 97403.

Proceedings of the National Academy of Sciences of the United States of America
|May 13, 2020
PubMed
Summary
This summary is machine-generated.

Researchers identified EPR-1, a protein essential for silencing genes marked by histone H3 lysine 27 (H3K27) methylation. Loss of EPR-1 de-represses these genes without affecting H3K27 methylation levels.

Keywords:
H3K27 methylationPolycomb repressive complexepigeneticsfacultative heterochromatinhistone reader

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Area of Science:

  • Molecular Biology
  • Genetics
  • Epigenetics

Background:

  • Histone H3 lysine 27 (H3K27) methylation is a key repressive chromatin mark.
  • The precise mechanism of H3K27 methylation-mediated gene silencing is not fully understood.

Purpose of the Study:

  • To identify novel factors involved in H3K27 methylation-mediated transcriptional repression.
  • To elucidate the mechanism of gene silencing by H3K27 methylation in *Neurospora crassa*.

Main Methods:

  • Forward genetic screen in *Neurospora crassa* to identify genes required for H3K27 methylation-dependent silencing.
  • Chromatin immunoprecipitation (ChIP) to assess protein association with H3K27-methylated chromatin.
  • Gene expression analysis to evaluate the impact of genetic modifications on target genes.

Main Results:

  • A bromo-adjacent homology (BAH)-plant homeodomain (PHD) protein, named EPR-1 (effector of polycomb repression 1), was identified.
  • EPR-1 physically associates with H3K27-methylated chromatin.
  • Loss of EPR-1 function leads to de-repression of H3K27-methylated genes, independent of H3K27 methylation levels.

Conclusions:

  • EPR-1 is a crucial component of the H3K27 methylation-mediated gene silencing pathway.
  • EPR-1 acts downstream or parallel to H3K27 methylation, mediating repression.
  • The presence of EPR-1 orthologs across eukaryotes suggests an evolutionarily conserved role in Polycomb group repression.