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Dynamic interplay and function of multiple noncoding genes governing X chromosome inactivation.

Minghui Yue1, John Lalith Charles Richard1, Yuya Ogawa1

  • 1Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.

Biochimica Et Biophysica Acta
|August 12, 2015
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Summary

Long noncoding RNAs (lncRNAs) regulate gene expression and X chromosome inactivation. This review details lncRNAs at the X inactivation center (Xic) and their role in establishing the inactive X chromosome

Keywords:
EpigeneticsLong noncoding RNAX-chromosome inactivationXist

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Area of Science:

  • Epigenetics
  • Genomics
  • Molecular Biology

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in gene regulation.
  • X chromosome inactivation establishes a unique epigenetic landscape on the inactive X chromosome (Xi) via the lncRNA Xist.
  • The X inactivation center (Xic) controls monoallelic Xist expression through topologically associated domains (TADs).

Purpose of the Study:

  • To review recent advances in understanding lncRNAs at the Xic.
  • To discuss the mechanisms by which lncRNAs at the Xic regulate X chromosome inactivation.
  • To explore the molecular basis of Xist RNA-mediated epigenetic changes on the Xi.

Main Methods:

  • Literature review of studies on lncRNAs, X chromosome inactivation, and epigenetic regulation.
  • Analysis of the roles of lncRNAs and proteins within Xic TADs.
  • Discussion of the molecular mechanisms of Xist RNA function.

Main Results:

  • lncRNAs are crucial regulators of gene expression and X chromosome inactivation.
  • Two distinct TADs within the Xic, involving lncRNAs like Xist and Tsix, tightly control monoallelic Xist expression.
  • Xist RNA is central to establishing the repressive epigenetic landscape of the Xi.

Conclusions:

  • lncRNAs at the Xic are key players in the precise regulation of X chromosome inactivation.
  • Understanding these lncRNAs and their interactions provides insight into epigenetic control.
  • Xist RNA's role in mediating epigenetic silencing is a critical aspect of X chromosome dosage compensation.