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HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge.

Abstract：

:It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.

journal_name

Nat Commun

journal_title

Nature communications

authors

Wang H,Cai H,Wang X,Zhang M,Liu B,Chen Z,Yang T,Fang J,Zhang Y,Liu W,Han J,Guo Q,Zhang H,Wang H,Xia G,Wang C

doi

10.1038/s41467-019-13671-8

subject

Has Abstract

pub_date

2019-12-16 00:00:00

pages

5719

issue

1

issn

2041-1723

pii

10.1038/s41467-019-13671-8

journal_volume

10

pub_type

杂志文章

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