Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells. (15th January 2021)

• Record Type: Journal Article
• Authors: Tamura, Isao; Maekawa, Ryo; Jozaki, Kosuke; Ohkawa, Yasuyuki; Takagi, Haruka; Doi-Tanaka, Yumiko; Shirafuta, Yuichiro; Mihara, Yumiko; Taketani, Toshiaki; Sato, Shun; Tamura, Hiroshi; Sugino, Norihiro
• Is Part Of: Molecular and cellular endocrinology. Volume 520(2021)
• Publication Date: 2021-01-15
• Subjects: Decidualization -- CCAAT enhancer-Binding protein β (C/EBPβ) -- p300 -- Endometrial stromal cells (ESCs) -- Histone acetylation; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2020.111085
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: We previously reported that H3K27 acetylation (H3K27ac) increases throughout the genome during decidualization of human endometrial stromal cells (ESCs). However, its mechanisms have not been clarified. We also reported that C/EBPβ acts as a pioneer factor initiating chromatin remodeling by increasing H3K27ac of IGFBP-1 and PRL promoters. Therefore, C/EBPβ may be involved in the genome-wide increase of H3K27ac during decidualization. In this study, we investigated whether C/EBPβ causes genome-wide H3K27ac modifications and regulates gene expressions during decidualization. cAMP was used to induce decidualization. Three types of cells (control cells, cAMP-treated cells, and cAMP-treated + C/EBPβ-knockdowned cells by siRNA) were generated. Of 4190 genes that were upregulated by cAMP, C/EBPβ knockdown inhibited these upregulation in 2239 genes (53.4%), indicating that they are under the regulation of C/EBPβ. cAMP increased H3K27ac in 1272 of the 2239 genes. C/EBPβ knockdown abolished the increase of H3K27ac in almost all genes (1263 genes, 99.3%), suggesting that C/EBPβ can upregulate gene expression by increasing H3K27ac. To investigate how C/EBPβ regulates H3K27ac throughout the genome, we tested the hypothesis that C/EBPβ binds to its binding regions and recruits cofactors with histone acetyltransferase activities. To do this, we collated our ChIP-sequence data with public ChIP-sequence database of transcription factors, and found that p300 is the most likely cofactor that binds to the H3K27ac-increased-regions with C/EBPβ. ChIP-qPCR of several genes confirmed that C/EBPβ binds to the target regions, recruits p300, and increases H3K27ac. Our genome-wide analysis revealed that C/EBPβ induces H3K27ac throughout the genome and upregulates gene expressions during decidualization by recruiting p300 to the promoters. Highlights: C/EBPβ regulates a number of gene expressions during decidualization. H3K27ac is induced by C/EBPb throughout the genome during decidualization. p300 is a cofactor of C/EBPβ inducing genome-wide H3K27ac. C/EBPβ acts as an epigenetic regulator of human endometrial stromal cells.