한빛사논문
University of Hong Kong (현 Weill Cornell Graduate School, Cornell University)
Jung Eun Kim 1, Xiyue Pan 1, Kwan Yiu Tse 1, Henry Hei Chan 1, Chao Dong 1,2 and Michael Shing Yan Huen 1,*
1School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong S.A.R.
2Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
*Corresponding author: correspondence to Michael Shing Yan Huen
Abstract
Transient halting of transcription activity on the damaged chromatin facilitates DNA double-strand break (DSB) repair. However, the molecular mechanisms that facilitate transcription recovery following DSB repair remain largely undefined. Notably, failure to restore gene expression in a timely manner can compromise transcriptome signatures and may impose deleterious impacts on cell identity and cell fate. Here, we report PHF8 as the major demethylase that reverses transcriptionally repressive epigenetic modification laid down by the DYRK1B–EHMT2 pathway. We found that PHF8 concentrates at laser-induced DNA damage tracks in a DYRK1B-dependent manner and promotes timely resolution of local H3K9me2 to facilitate the resumption of transcription. Moreover, PHF8 also assists in the recovery of ribosomal DNA (rDNA) transcription following the repair of nucleolar DSBs. Taken together, our findings uncover PHF8 as a key mediator that coordinates transcription activities during the recovery phase of DSB responses.
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