Ovulatory Signal-triggered Chromatin Remodeling in Ovarian Granulosa Cells by HDAC2 Phosphorylation Activation-mediated Histone Deacetylation

Overview

Journal Epigenetics Chromatin

Publisher Biomed Central

Specialties Biochemistry
Genetics

Date 2023 Apr 19

PMID 37076890

Authors

Jiamin Jin

Peipei Ren

Xiang Li

Yinyi Zhang

Weijie Yang

Yerong Ma

Mengru Lai

Chao Yu

Songying Zhang

Yin-Li Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Epigenetic reprogramming is involved in luteinizing hormone (LH)-induced ovulation; however, the underlying mechanisms are largely unknown.

Results: We here observed a rapid histone deacetylation process between two waves of active transcription mediated by the follicle-stimulating hormone (FSH) and the LH congener human chorionic gonadotropin (hCG), respectively. Analysis of the genome-wide H3K27Ac distribution in hCG-treated granulosa cells revealed that a rapid wave of genome-wide histone deacetylation remodels the chromatin, followed by the establishment of specific histone acetylation for ovulation. HDAC2 phosphorylation activation coincides with histone deacetylation in mouse preovulatory follicles. When HDAC2 was silenced or inhibited, histone acetylation was retained, leading to reduced gene transcription, retarded cumulus expansion, and ovulation defect. HDAC2 phosphorylation was associated with CK2α nuclear translocation, and inhibition of CK2α attenuated HDAC2 phosphorylation, retarded H3K27 deacetylation, and inactivated the ERK1/2 signaling cascade.

Conclusions: This study demonstrates that the ovulatory signal erases histone acetylation through activation of CK2α-mediated HDAC2 phosphorylation in granulosa cells, which is an essential prerequisite for subsequent successful ovulation.

Citing Articles

Cellular atlas of the human ovary using morphologically guided spatial transcriptomics and single-cell sequencing.

Jones A, Hannum D, Machlin J, Tan A, Ma Q, Ulrich N Sci Adv. 2024; 10(14):eadm7506.

PMID: 38578993 PMC: 10997207. DOI: 10.1126/sciadv.adm7506.

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