Transcription recovery after DNA damage requires chromatin priming by the H3.3 histone chaperone HIRA.
Understanding how to recover fully functional and transcriptionally active chromatin when its integrity has been challenged by genotoxic stress is a critical issue. Here, by investigating how chromatin dynamics regulate transcriptional activity in response to DNA damage in human cells, we identify a pathway involving the histone chaperone histone regulator A (HIRA) to promote transcription restart after UVC damage. Our mechanistic studies reveal that HIRA accumulates at sites of UVC irradiation upon detection of DNA damage prior to repair and deposits newly synthesized H3.3 histones. This local action of HIRA depends on ubiquitylation events associated with damage recognition. Furthermore, we demonstrate that the early and transient function of HIRA in response to DNA damage primes chromatin for later reactivation of transcription. We propose that HIRA-dependent histone deposition serves as a chromatin bookmarking system to facilitate transcription recovery after genotoxic stress.
Chromatin Dynamics, Institut Curie Research Centre, 75248 Paris Cedex 5, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 218, 75248 Paris Cedex 5, France.
Salomé
S
Adam
Sophie E
SE
Polo
Geneviève
G
Almouzni
D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin; D004249:DNA Damage / Q000528:radiation effects*; D004260:DNA Repair; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D054875:Ubiquitination; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D002843:Chromatin; C086057:HIRA protein, human; D056488:Histone Chaperones; D006657:Histones; D014157:Transcription Factors