Transcription factor C/EBPβ induces genome-wide H3K27ac and upregulates gene expression during decidualization of human endometrial stromal cells

Isao Tamura, Ryo Maekawa, Kosuke Jozaki, Yasuyuki Ohkawa, Haruka Takagi, Yumiko Doi-Tanaka, Yuichiro Shirafuta, Yumiko Mihara, Toshiaki Taketani, Shun Sato, Hiroshi Tamura, Norihiro Sugino

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number111085
JournalMolecular and Cellular Endocrinology
Volume520
DOIs
Publication statusPublished - Jan 15 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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