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


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.

SUBMITTER: Sangrithi MN 

PROVIDER: S-EPMC5300051 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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

Sangrithi Mahesh N MN   Royo Helene H   Mahadevaiah Shantha K SK   Ojarikre Obah O   Bhaw Leena L   Sesay Abdul A   Peters Antoine H F M AH   Stadler Michael M   Turner James M A JM  

Developmental cell 20170126 3


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, consis  ...[more]

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