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

Publication date: Available online 26 January 2017
Source:Developmental Cell
Author(s): Mahesh N. Sangrithi, Helene Royo, Shantha K. Mahadevaiah, Obah Ojarikre, Leena Bhaw, Abdul Sesay, Antoine H.F.M. Peters, Michael Stadler, James M.A. Turner
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.

Teaser

Germ cells reset their epigenome and transcriptome prior to meiosis. Sangrithi et al. show that unique X chromosome dosage compensation states prevail in germ cells. These states are determined by the number of X chromosomes present rather than phenotypic sex, providing a different perspective on infertility associated with sex chromosome aneuploidy.


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