The CtIP-CtBP1/2-HDAC1-AP1 transcriptional complex is required for the transrepression of DNA damage modulators in the pathogenesis of osteosarcoma.

ABSTRACT: Most tumors, including osteosarcomas, have deficiencies in DNA damage repair. However, the regulatory mechanisms underlying dysregulation of DNA damage repair genes are still being investigated. In this study, we reveal that C-terminal binding protein (CtBP) interacting protein (CtIP) couples with three transcriptional regulators, CtBP1/2 heterodimer, histone deacetylase 1 (HDAC1), and two subunits of the activating protein 1 (AP1) transcription factor to assemble a transcriptional complex. This complex specifically controls the expression of four genes involved in DNA damage and repair processes: MutL homolog 1 (MLH1), MutS Homolog 3 (MSH3), breast cancer type 1 (BRCA1), and cyclin dependent kinase inhibitor 1A (CDKN1A). Chromatin immunoprecipitation (ChIP) assay results revealed that the

SUBMITTER: Chen X 

PROVIDER: S-EPMC9047009 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature