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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Epigenetic events regulating monoallelic gene expression.

Shabnam Massah1, Timothy V Beischlag1, Gratien G Prefontaine1

  • 1a The Faculty of Health Sciences , Simon Fraser University , Burnaby , BC , Canada.

Critical Reviews in Biochemistry and Molecular Biology
|July 10, 2015
PubMed
Summary

Mammals exhibit monoallelic gene expression, where only one gene copy is active. Epigenetic mechanisms regulate this process, crucial for development and preventing diseases.

Keywords:
Allelic exclusionDNA methylationX-chromosome inactivationepigeneticsgene regulationhistone modificationsmonoallelic gene expressionprotocadherin

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Area of Science:

  • Genetics and Epigenetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Mammalian gene expression typically involves similar levels from both parental alleles.
  • A significant percentage (6-10%) of non-sex chromosome genes undergo monoallelic expression.
  • This selective gene expression, or allelic exclusion, can be parent-specific (imprinted) or random (stochastic).

Purpose of the Study:

  • To review the current understanding of monoallelic gene expression.
  • To explore the molecular mechanisms governing allelic exclusion.
  • To focus on three key classes: X-linked genes, imprinted genes, and protocadherin (PCDH) genes.

Main Methods:

  • Review of existing literature on gene expression and epigenetic regulation.
  • Analysis of molecular mechanisms including DNA methylation, histone modifications, chromatin interactions, and non-coding RNAs.
  • Categorization of monoallelically expressed genes into X-linked, imprinted, and PCDH classes.

Main Results:

  • Monoallelic expression is a common regulatory strategy in mammals, established via imprinted or stochastic mechanisms.
  • Epigenetic factors like DNA methylation, histone modifications, chromatin interactions, and ncRNAs are critical regulators.
  • Dysregulation of allelic exclusion is linked to developmental disorders.

Conclusions:

  • Epigenetic mechanisms play a fundamental role in establishing and maintaining monoallelic gene expression.
  • Understanding these mechanisms is vital for normal development and preventing associated diseases.
  • This review synthesizes knowledge on monoallelic expression, focusing on X-linked, imprinted, and PCDH genes.