RT Journal Article
SR Electronic
T1 X-chromosome upregulation is dynamically linked to the X-inactivation state
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.06.189787
DO 10.1101/2020.07.06.189787
A1 Antonio Lentini
A1 Christos Coucoravas
A1 Nathanael Andrews
A1 Martin Enge
A1 Qiaolin Deng
A1 Björn Reinius
YR 2020
UL http://biorxiv.org/content/early/2020/08/04/2020.07.06.189787.abstract
AB Mammalian X-chromosome dosage balance is regulated by X-chromosome inactivation (XCI) and X-chromosome upregulation (XCU), but the dynamics of XCU as well as the interplay between the two mechanisms remain poorly understood. Here, we mapped XCU throughout early mouse embryonic development at cellular and allelic resolution, revealing sex- and lineage-specific dynamics along key events in X-chromosome regulation. Our data show that XCU is linearly proportional to the degree of XCI, indicating that dosage compensation ensues based on mRNA levels rather than number of active X chromosomes. In line with this, we reveal that the two active X chromosomes in female naïve embryonic stem cells are not hyperactive as previously thought. In all lineages, XCU was underlain by increased transcriptional burst frequencies, providing a mechanistic basis in vivo. Together, our results demonstrate unappreciated flexibility of XCU in balancing X-chromosome expression, and we propose a general model for allelic dosage balance, applicable for wider mechanisms of transcriptional regulation.Competing Interest StatementThe authors have declared no competing interest.