title: H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells.
abstract: The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.
authors.affiliation: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus, Jerusalem, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Hezroni
authors.forename: Itai
authors.initials: I
authors.lastname: Tzchori
authors.forename: Anna
authors.initials: A
authors.lastname: Davidi
authors.forename: Anna
authors.initials: A
authors.lastname: Mattout
authors.forename: Alva
authors.initials: A
authors.lastname: Biran
authors.forename: Malka
authors.initials: M
authors.lastname: Nissim-Rafinia
authors.forename: Heiner
authors.initials: H
authors.lastname: Westphal
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
mesh_terms: D000107:Acetylation; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002460:Cell Line; D065150:Cellular Reprogramming / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases