Chd1 protects genome integrity at promoters to sustain hypertranscription in embryonic stem cells
نویسندگان
چکیده
Abstract Stem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 mediates hypertranscription in pluripotent but its mechanism action remains poorly understood. Here we report novel role for protecting genome integrity at promoter regions by preventing DNA double-stranded break (DSB) accumulation ES cells. interacts with several repair factors including Atm, Parp1, Kap1 Topoisomerase 2β absence leads to an DSBs Chd1-bound Pol II-transcribed genes rDNA. Genes prone breaks KO are longer GC-rich promoters, more labile nucleosomal structure roles regulation, transcription signaling. These results reveal vulnerability hypertranscribing stem endogenous breaks, important implications cancer biology.
منابع مشابه
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ژورنال
عنوان ژورنال: Nature Communications
سال: 2021
ISSN: ['2041-1723']
DOI: https://doi.org/10.1038/s41467-021-25088-3