FeaSion decodes the regulatory landscape and functional diversity of RNA polymerase II CTD phosphorylation.

ABSTRACT: RNA polymerase II's (RNAPII) C-terminal domain (CTD) contains five phosphorylation sites (pY1, pS2, pT4, pS5, and pS7). However, their regulatome and immediate functions remain elusive. Using the FeaSion (Feature-Screening-Function) strategy, we mapped RNAPII phosphorylation site-specific interactors and genomic occupancy, revealing links to preferential gene length, exon number, and transcription factor binding. CRISPR-FACS screens identified different candidate regulators modulating individual phosphorylation sites. Rapid replacement showed site-specific mutations influence different transcriptional processes, histone modifications (H3K36me3 and H2A.Zac), and preferentially affect developmental and signaling genes. Moreover, we demonstrate kinases CLK1/4 and YES1 directly regulate RNAPII

SUBMITTER: Zhu J 

PROVIDER: S-EPMC12662217 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature