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Publication : Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.

First Author  Li-Bao L Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  3931
PubMed ID  38729993 Mgi Jnum  J:348281
Mgi Id  MGI:7640852 Doi  10.1038/s41467-024-48258-5
Citation  Li-Bao L, et al. (2024) Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression. Nat Commun 15(1):3931
abstractText  MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.
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