Dicer promotes genome stability via the bromodomain transcriptional co-activator BRD4.

ABSTRACT: RNA interference is required for post-transcriptional silencing, but also has additional roles in transcriptional silencing of centromeres and genome stability. However, these roles have been controversial in mammals. Strikingly, we found that Dicer-deficient embryonic stem cells have strong proliferation and chromosome segregation defects as well as increased transcription of centromeric satellite repeats, which triggers the interferon response. We conducted a CRISPR-Cas9 genetic screen to restore viability and identified transcriptional activators, histone H3K9 methyltransferases, and chromosome segregation factors as suppressors, resembling Dicer suppressors identified in independent screens in fission yeast. The strongest suppressors were mutations in the transcriptional co-activator B

SUBMITTER: Gutbrod MJ 

PROVIDER: S-EPMC8863982 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature