title: Epigenetically coordinated GATA2 binding is necessary for endothelium-specific endomucin expression.
abstract: GATA2 is well recognized as a key transcription factor and regulator of cell-type specificity and differentiation. Here, we carried out comparative chromatin immunoprecipitation with comprehensive sequencing (ChIP-seq) to determine genome-wide occupancy of GATA2 in endothelial cells and erythroids, and compared the occupancy to the respective gene expression profile in each cell type. Although GATA2 was commonly expressed in both cell types, different GATA2 bindings and distinct cell-specific gene expressions were observed. By using the ChIP-seq with epigenetic histone modifications and chromatin conformation capture assays; we elucidated the mechanistic regulation of endothelial-specific GATA2-mediated endomucin gene expression, that was regulated by the endothelial-specific chromatin loop with a GATA2-associated distal enhancer and core promoter. Knockdown of endomucin markedly attenuated endothelial cell growth, migration and tube formation. Moreover, abrogation of GATA2 in endothelium demonstrated not only a reduction of endothelial-specific markers, but also induction of mesenchymal transition promoting gene expression. Our findings provide new insights into the correlation of endothelial-expressed GATA2 binding, epigenetic modification, and the determination of endothelial cell specificity.
authors.affiliation: LSBM, The Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Kanki
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.forename: Shuying
authors.initials: S
authors.lastname: Jiang
authors.forename: Shuichi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Imari
authors.initials: I
authors.lastname: Mimura
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suehiro
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohta
authors.forename: Sigeo
authors.initials: S
authors.lastname: Ihara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Takashi
authors.initials: T
authors.lastname: Minami
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology*; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D020014:K562 Cells; D046228:Microarray Analysis; D008954:Models, Biological; D009928:Organ Specificity / Q000187:drug effects / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C431275:EMCN protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D034741:RNA, Small Interfering; D012795:Sialoglycoproteins