Self-renewal and pluripotency of the embryonic stem cell (ESC) state are established and maintained by multiple regulatory networks that comprise transcription factors and epigenetic regulators. While much has been learned regarding transcription factors, the function of epigenetic regulators in these networks is less well defined. We conducted a CRISPR-Cas9-mediated loss-of-function genetic screen that identified two epigenetic regulators, TAF5L and TAF6L, components or co-activators of the GNAT-HAT complexes for the mouse ESC (mESC) state. Detailed molecular studies demonstrate that TAF5L/TAF6L transcriptionally activate c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks. Besides, TAF5L/TAF6L predominantly regulate their target genes through H3K9ac deposition and c-MYC recruitment that eventually activate the MYC regulatory network for self-renewal of mESCs. Thus, our findings uncover a role of TAF5L/TAF6L in directing the MYC regulatory network that orchestrates gene expression programs to control self-renewal for the maintenance of mESC state.
Pubmed ID: 31005419 RIS Download
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Bioinformatics 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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View all literature mentionsMus musculus with name B6;129S4-Pou5f1tm2Jae/J from IMSR.
View all literature mentionsMus musculus with name B6;129S4-Col1a1tm1(tetO-Pou5f1.-Klf4.-Sox2.-Myc)Hoch/J from IMSR.
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View all literature mentionsCell line J1 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsMus musculus with name B6;129S4-Pou5f1tm2Jae/J from IMSR.
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View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line J1 is a Embryonic stem cell with a species of origin Mus musculus (Mouse)
View all literature mentionsThis monoclonal targets CTD of RNA polymerase II
View all literature mentionsThis monoclonal targets Ser2-P of RNA polymerase II
View all literature mentionsThis monoclonal targets Ser5-P of RNA polymerase II
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View all literature mentionsThis polyclonal targets c-Myc
View all literature mentionsThis polyclonal targets POU5F1
View all literature mentions