Ash2L enables P53-dependent apoptosis by favoring stable transcription pre-initiation complex formation on its pro-apoptotic target promoters.

ABSTRACT: Chromatin conformation has a major role in all cellular decisions. We showed previously that P53 pro-apoptotic target promoters are enriched with H3K9me3 mark and induction of P53 abrogates this repressive chromatin conformation by downregulating SUV39H1, the writer of this mark present on these promoters. In the present study, we demonstrate that in response to P53 stabilization, its pro-apoptotic target promoters become enriched with the H3K4me3 epigenetic mark as well as its readers, Wdr5, RbBP5 and Ash2L, which were not observed in response to SUV39H1 downregulation alone. Overexpression of Ash2L enhanced P53-dependent apoptosis in response to chemotherapy, associated with increased P53 pro-apoptotic gene promoter occupancy and target gene expression. In contrast, pre-silencing of Ash2

SUBMITTER: Mungamuri SK 

PROVIDER: S-EPMC4295002 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature