The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of α-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit.
Pubmed ID: 27939217 RIS Download
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This monoclonal targets Histone H3.3
View all literature mentionsThis monoclonal targets HIRA
View all literature mentionsThis polyclonal targets Brachyury / Bry - Mesoderm Marker
View all literature mentionsThis monoclonal targets HIRA antibody [EPR7416]
View all literature mentionsThis monoclonal targets HIRA clone WC119
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View all literature mentionsThis polyclonal targets Histone H3 (di methyl K9 + K9)
View all literature mentionsThis polyclonal targets Histone H3 (di methyl K27)
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View all literature mentionsThis polyclonal targets IDH3G
View all literature mentionsThis monoclonal targets IDH3B (V-13)
View all literature mentionsThis polyclonal targets Idh3a
View all literature mentionsThis monoclonal targets IDH2 antibody [EPR7577]
View all literature mentionsThis polyclonal targets Histone H4 (tri methyl K20) - ChIP Grade
View all literature mentionsThis polyclonal targets HA tag - ChIP Grade
View all literature mentionsThis polyclonal targets Histone H4
View all literature mentionsThis polyclonal targets H3K9me3
View all literature mentionsThis polyclonal targets H3K27me2
View all literature mentionsThis monoclonal targets Histone H3 (tri methyl K27) antibody [mAbcam 6002] - ChIP Grade
View all literature mentionsThis polyclonal targets H3K4me1
View all literature mentionsThis polyclonal targets H3K4me2
View all literature mentionsThis polyclonal targets Histone H3 (tri methyl K4)
View all literature mentionsThis monoclonal targets Oct-3/4
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View all literature mentionsThis unknown targets goat-IgG-control
View all literature mentionsThis polyclonal targets PHB
View all literature mentionsA clustering software package for identification of enriched domains from histone modification ChIP-Seq data.
View all literature mentionsBioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
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