Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation
Journal
Nature Cell Biology
Journal Volume
22
Journal Issue
12
Start Page
1436
End Page
1446
ISSN
1465-7392
Date Issued
2020-11-30
Author(s)
Chitiashvili, Tsotne
Dror, Iris
Kim, Rachel
Chaudhari, Rohan
Pandolfi, Erica
Chen, Di
Liebscher, Simone
Schenke-Layland, Katja
Plath, Kathrin
Clark, Amander
Abstract
X-chromosome dosage compensation in female placental mammals is achieved by X-chromosome inactivation (XCI). Human pre-implantation embryos are an exception, in which dosage compensation occurs by X-chromosome dampening (XCD). Here, we examined whether XCD extends to human prenatal germ cells given their similarities to naive pluripotent cells. We found that female human primordial germ cells (hPGCs) display reduced X-linked gene expression before entering meiosis. Moreover, in hPGCs, both X chromosomes are active and express the long non-coding RNAs X active coating transcript (XACT) and X inactive specific transcript (XIST)—the master regulator of XCI—which are silenced after entry into meiosis. We find that XACT is a hPGC marker, describe XCD associated with XIST expression in hPGCs and suggest that XCD evolved in humans to regulate X-linked genes in pre-implantation embryos and PGCs. Furthermore, we found a unique mechanism of X-chromosome regulation in human primordial oocytes. Therefore, future studies of human germline development must consider the sexually dimorphic X-chromosome dosage compensation mechanisms in the prenatal germline.
Subjects
long untranslated RNA
XIST non-coding RNA
Publisher
Nature Research
Type
journal article