PMID- 31844300 OWN - NLM STAT- MEDLINE DCOM- 20200402 LR - 20210110 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 10 IP - 1 DP - 2019 Dec 16 TI - HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge. PG - 5719 LID - 10.1038/s41467-019-13671-8 [doi] LID - 5719 AB - 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. FAU - Wang, Huarong AU - Wang H AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. AD - Medical College of Xiamen University, 361005, Xiamen, China. FAU - Cai, Han AU - Cai H AD - Medical College of Xiamen University, 361005, Xiamen, China. FAU - Wang, Xiao AU - Wang X AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. AD - Beijing Advanced Innovation Center for Genomics, Biomedical Pioneering Innovation Center, College of Life Sciences, Peking University, 100871, Beijing, China. FAU - Zhang, Meiling AU - Zhang M AD - Shanghai Key Laboratory for Assistant Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 200127, Shanghai, China. FAU - Liu, Bingying AU - Liu B AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Chen, Ziqi AU - Chen Z AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Yang, Tingting AU - Yang T AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Fang, Junshun AU - Fang J AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. AD - Reproductive Medical Center, Drum Tower Hospital Affiliated to Nanjing University Medical College, Zhongshan Road 321, 210008, Nanjing, China. FAU - Zhang, Yanhao AU - Zhang Y AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Liu, Wei AU - Liu W AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Han, Jun AU - Han J AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Guo, Qirui AU - Guo Q AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Zhang, Hua AU - Zhang H AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. FAU - Wang, Haibin AU - Wang H AD - Medical College of Xiamen University, 361005, Xiamen, China. FAU - Xia, Guoliang AU - Xia G AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. AD - Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, College of Life Science, Ningxia University, 750021, Yinchuan, Ningxia, China. FAU - Wang, Chao AU - Wang C AD - State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, China. wangcam@cau.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191216 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (Forkhead Box Protein O1) RN - 0 (Foxo1 protein, mouse) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Histones) RN - 0 (Sp1 Transcription Factor) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 3.5.1.98 (Histone Deacetylases) RN - EC 3.5.1.98 (histone deacetylase 3) SB - IM MH - Acetylation MH - Amphiregulin/*genetics MH - Animals MH - Cells, Cultured MH - Female MH - Forkhead Box Protein O1/metabolism MH - *Gene Expression Regulation, Developmental MH - Gene Knockout Techniques MH - Granulosa Cells/metabolism MH - Histone Deacetylase Inhibitors/pharmacology MH - Histone Deacetylases/genetics/*metabolism MH - Histones/metabolism MH - Luteinizing Hormone/metabolism MH - Meiosis/*genetics MH - Mice MH - Oocytes/*growth & development MH - Oogenesis/drug effects/*genetics MH - Primary Cell Culture MH - Promoter Regions, Genetic/genetics MH - Sp1 Transcription Factor/metabolism PMC - PMC6915726 COIS- The authors declare no competing interests. EDAT- 2019/12/18 06:00 MHDA- 2020/04/03 06:00 PMCR- 2019/12/16 CRDT- 2019/12/18 06:00 PHST- 2018/11/06 00:00 [received] PHST- 2019/11/18 00:00 [accepted] PHST- 2019/12/18 06:00 [entrez] PHST- 2019/12/18 06:00 [pubmed] PHST- 2020/04/03 06:00 [medline] PHST- 2019/12/16 00:00 [pmc-release] AID - 10.1038/s41467-019-13671-8 [pii] AID - 13671 [pii] AID - 10.1038/s41467-019-13671-8 [doi] PST - epublish SO - Nat Commun. 2019 Dec 16;10(1):5719. doi: 10.1038/s41467-019-13671-8.