Imprinted X chromosome inactivation at the gamete-to-embryo transition.

Autor:	Wei C; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA., Kesner B; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA., Yin H; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA., Lee JT; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. Electronic address: lee@molbio.mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Apr 18; Vol. 84 (8), pp. 1442-1459.e7. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1016/j.molcel.2024.02.013
Abstrakt:	In mammals, dosage compensation involves two parallel processes: (1) X inactivation, which equalizes X chromosome dosage between males and females, and (2) X hyperactivation, which upregulates the active X for X-autosome balance. The field currently favors models whereby dosage compensation initiates "de novo" during mouse development. Here, we develop "So-Smart-seq" to revisit the question and interrogate a comprehensive transcriptome including noncoding genes and repeats in mice. Intriguingly, de novo silencing pertains only to a subset of Xp genes. Evolutionarily older genes and repetitive elements demonstrate constitutive Xp silencing, adopt distinct signatures, and do not require Xist to initiate silencing. We trace Xp silencing backward in developmental time to meiotic sex chromosome inactivation in the male germ line and observe that Xm hyperactivation is timed to Xp silencing on a gene-by-gene basis. Thus, during the gamete-to-embryo transition, older Xp genes are transmitted in a "pre-inactivated" state. These findings have implications for the evolution of imprinting. Competing Interests: Declaration of interests J.T.L. is a cofounder of Fulcrum Therapeutics and an advisor to Skyhawk Therapeutics. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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