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Dev Cell. 2017 Feb 6;40(3):289-301.e3. doi: 10.1016/j.devcel.2016.12.023. Epub 2017 Jan 26.

Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline.

Author information

1
Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK; UCL EGA Institute for Women's Health UCL, Medical School Building, 74 Huntley Street, London WC1E 6AU, UK.
2
Friedrich Miescher Institute for Biomedical Research (FMI), 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland.
3
Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK.
4
Friedrich Miescher Institute for Biomedical Research (FMI), 4058 Basel, Switzerland.
5
Mill Hill Laboratory, The Francis Crick Institute, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: james.turner@crick.ac.uk.

Abstract

Somatic X dosage compensation requires two mechanisms: X inactivation balances X gene output between males (XY) and females (XX), while X upregulation, hypothesized by Ohno and documented in vivo, balances X gene with autosomal gene output. Whether X dosage compensation occurs in germ cells is unclear. We show that mouse and human germ cells exhibit non-canonical X dosage states that differ from the soma and between the sexes. Prior to genome-wide reprogramming, X upregulation is present, consistent with Ohno's hypothesis. Subsequently, however, it is erased. In females, erasure follows loss of X inactivation, causing X dosage excess. Conversely, in males, erasure leads to permanent X dosage decompensation. Sex chromosomally abnormal models exhibit a "sex-reversed" X dosage state: XX males, like XX females, develop X dosage excess, while XO females, like XY males, develop X dosage decompensation. Thus, germline X dosage compensation states are determined by X chromosome number, not phenotypic sex. These unexpected differences in X dosage compensation states between germline and soma offer unique perspectives on sex chromosome infertility.

KEYWORDS:

X inactivation; X upregulation; dosage compensation; genome-wide reprogramming; germline development; sex chromosomes

PMID:
28132849
PMCID:
PMC5300051
DOI:
10.1016/j.devcel.2016.12.023
[Indexed for MEDLINE]
Free PMC Article

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