PMID- 18614019 OWN - NLM STAT- MEDLINE DCOM- 20080725 LR - 20211020 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 134 IP - 1 DP - 2008 Jul 11 TI - An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of embryonic stem cell identity. PG - 162-74 LID - 10.1016/j.cell.2008.05.031 [doi] AB - Proper regulation of chromatin structure is necessary for the maintenance of cell type-specific gene expression patterns. The embryonic stem cell (ESC) expression pattern governs self-renewal and pluripotency. Here, we present an RNAi screen in mouse ESCs of 1008 loci encoding chromatin proteins. We identified 68 proteins that exhibit diverse phenotypes upon knockdown (KD), including seven subunits of the Tip60-p400 complex. Phenotypic analyses revealed that Tip60-p400 is necessary to maintain characteristic features of ESCs. We show that p400 localization to the promoters of both silent and active genes is dependent upon histone H3 lysine 4 trimethylation (H3K4me3). Furthermore, the Tip60-p400 KD gene expression profile is enriched for developmental regulators and significantly overlaps with that of the transcription factor Nanog. Depletion of Nanog reduces p400 binding to target promoters without affecting H3K4me3 levels. Together, these data indicate that Tip60-p400 integrates signals from Nanog and H3K4me3 to regulate gene expression in ESCs. FAU - Fazzio, Thomas G AU - Fazzio TG AD - Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA. thomas.fazzio@ucsf.edu FAU - Huff, Jason T AU - Huff JT FAU - Panning, Barbara AU - Panning B LA - eng SI - GEO/GSE11243 GR - R01 GM063671/GM/NIGMS NIH HHS/United States GR - R01 GM085186/GM/NIGMS NIH HHS/United States GR - R01 GM085186-01A1/GM/NIGMS NIH HHS/United States GR - R01 GM63671/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Calcium Channels) RN - 0 (Histones) RN - 0 (Homeodomain Proteins) RN - 0 (Inositol 1,4,5-Trisphosphate Receptors) RN - 0 (Itpr1 protein, mouse) RN - 0 (Nanog Homeobox Protein) RN - 0 (Nanog protein, mouse) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Trans-Activators) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (Kat5 protein, mouse) RN - EC 2.3.1.48 (Lysine Acetyltransferase 5) SB - IM MH - Animals MH - Calcium Channels/*metabolism MH - Embryonic Stem Cells/cytology/*metabolism MH - Histone Acetyltransferases/*metabolism MH - Histones/metabolism MH - Homeodomain Proteins/metabolism MH - Inositol 1,4,5-Trisphosphate Receptors MH - Lysine Acetyltransferase 5 MH - Mice MH - Nanog Homeobox Protein MH - Promoter Regions, Genetic MH - RNA Interference MH - Receptors, Cytoplasmic and Nuclear/*metabolism MH - Trans-Activators MH - Transcription, Genetic PMC - PMC4308735 MID - NIHMS190735 EDAT- 2008/07/11 09:00 MHDA- 2008/07/26 09:00 PMCR- 2015/01/28 CRDT- 2008/07/11 09:00 PHST- 2007/11/28 00:00 [received] PHST- 2008/03/04 00:00 [revised] PHST- 2008/05/01 00:00 [accepted] PHST- 2008/07/11 09:00 [pubmed] PHST- 2008/07/26 09:00 [medline] PHST- 2008/07/11 09:00 [entrez] PHST- 2015/01/28 00:00 [pmc-release] AID - S0092-8674(08)00692-2 [pii] AID - 10.1016/j.cell.2008.05.031 [doi] PST - ppublish SO - Cell. 2008 Jul 11;134(1):162-74. doi: 10.1016/j.cell.2008.05.031.