Non-canonical and sexually dimorphic X dosage compensation states in the mouse and human germline

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1-s2.0-S1534580716309182-main.pdf (2.88 MB)

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OA Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300051/

Author(s)

Sangrithi, MN

Royo, H

Mahadevaiah, SK

Ojarikre, O

Bhaw, L

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Type

Journal Article

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.

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Date Issued

2017-01-26

Date Acceptance

2016-12-27

Citation

Developmental Cell, 2017, 40 (3), pp.289-301

URI

http://hdl.handle.net/10044/1/51133

DOI

https://www.dx.doi.org/10.1016/j.devcel.2016.12.023

ISSN

1534-5807

Publisher

Elsevier

Start Page

289

End Page

301

Journal / Book Title

Developmental Cell

Volume

40

Issue

3

Copyright Statement

© 2017 The Francis Crick Institute. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Identifier

http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000393735400009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202

Subjects

Science & Technology

Life Sciences & Biomedicine

Cell Biology

Developmental Biology

SEX-CHROMOSOME INACTIVATION

UP-REGULATION

LINKED GENES

Y-CHROMOSOMES

CELL SPECIFICATION

MAMMALIAN MEIOSIS

RNA-SEQ

EXPRESSION

MICE

EVOLUTION

Publication Status

Published