title: Genome-wide analysis of histone modifications in human endometrial stromal cells.
abstract: Dramatic changes of gene expressions occur in human endometrial stromal cells (ESCs) during decidualization. The changes in gene expression are associated with changes of chromatin structure, which are regulated by histone modifications. Here we investigated genome-wide changes in histone modifications associated with decidualization in human ESCs using chromatin immunoprecipitation combined with next-generation sequencing. ESCs were incubated with estradiol and medroxyprogesterone acetate for 14 days to induce decidualization. The chromatin immunoprecipitation-sequence data showed that induction of decidualization increased H3K27ac and H3K4me3 signals in many genomic regions but decreased in only a few regions. Most of the H3K27ac-increased regions (80%) and half of the H3K4me3-increased regions were located in the distal promoter regions (more than 3 kb upstream or downstream of the transcription start site). RNA sequence showed that induction of decidualization up-regulated 881 genes, 223 of which had H3K27ac- or H3K4me3-increased regions in the proximal and distal promoter regions. Induction of decidualization increased the mRNA levels of these genes more than it increased the mRNA levels of genes without H3K27ac- or H3K4me3-increased regions. Pathway analysis revealed that up-regulated genes with the H3K27ac- or H3K4me3-increased regions were associated with the insulin signaling, which may be involved in glucose uptake that is necessary for ESCs to undergo decidualization. These results show that histone modification statuses on a genome-wide basis change in human ESCs during decidualization. The main changes of histone modifications are increases of H3K27ac and H3K4me3 in both the proximal and distal promoter regions, which are involved in the up-regulation of gene expression that occurs during decidualization.
authors: Department of Obstetrics and Gynecology (I.T., K.J., M.O., L.L., R.M., H.A., S.S., Y.Y., H.T., N.S.), Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; Department of Advanced Initiative Medicine (Y.O.), Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka, 812-8582, Japan; and Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
authors: Isao
authors: I
authors: Tamura
authors: Yasuyuki
authors: Y
authors: Ohkawa
authors: Tetsuya
authors: T
authors: Sato
authors: Mikita
authors: M
authors: Suyama
authors: Kosuke
authors: K
authors: Jozaki
authors: Maki
authors: M
authors: Okada
authors: Lifa
authors: L
authors: Lee
authors: Ryo
authors: R
authors: Maekawa
authors: Hiromi
authors: H
authors: Asada
authors: Shun
authors: S
authors: Sato
authors: Yoshiaki
authors: Y
authors: Yamagata
authors: Hiroshi
authors: H
authors: Tamura
authors: Norihiro
authors: N
authors: Sugino
mesh_terms: D000328:Adult; D003656:Decidua / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D006657:Histones; D007328:Insulin