AI Article Synopsis
- The study explores how embryonic stem cells (ESC) maintain their ability to self-renew and remain pluripotent through regulatory networks involving transcription factors and epigenetic regulators.
- Researchers used a CRISPR-Cas9 screening method to identify two epigenetic regulators, TAF5L and TAF6L, that are crucial for the maintenance of mouse ESC (mESC) states.
- TAF5L and TAF6L were found to activate key genes like c-Myc and Oct4, using mechanisms such as H3K9ac deposition, influencing the MYC regulatory network essential for the self-renewal of mESCs.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671628 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2019.03.025 | DOI Listing |
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