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Suppression and recovery of BRCA1-mediated transcription by HP1? via modulation of promoter occupancy.

ABSTRACT: Heterochromatin protein 1? (HP1?) is a chromatin protein involved in gene silencing. Herein, we show that HP1? interacts with breast cancer type 1 susceptibility protein (BRCA1) and regulates BRCA1-mediated transcription via modulation of promoter occupancy and histone modification. We used several HP1? mutants and small interfering RNAs for histone methyltransferases to show that BRCA1-HP1? interaction, but not methylated histone binding, is important in HP1? repression of BRCA1-mediated transcription. Time-lapse studies on promoter association and histone methylation after DNA damage revealed that HP1? accumulates at the promoter before DNA damage, but BRCA1 is recruited at the promoter after the damage while promoter-resident HP1? is disassembled. Importantly, HP1? assembly recovers after release from the damage in a BRCA1-HP1? interaction-dependent manner and targets SUV39H1. HP1?/SUV39H1 restoration at the promoter results in BRCA1 disassembly and histone methylation, after which transcription repression resumes. We propose that through interaction with BRCA1, HP1? is guided to the BRCA1 target promoter during recovery and functions in the activation-repression switch and recovery from BRCA1-mediated transcription in response to DNA damage.

SUBMITTER: Choi JD

PROVIDER: S-EPMC3526311 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Suppression and recovery of BRCA1-mediated transcription by HP1γ via modulation of promoter occupancy.

Choi Jae Duk JD Park Mi Ae MA Lee Jong-Soo JS

Nucleic acids research 20121015 22

Heterochromatin protein 1γ (HP1γ) is a chromatin protein involved in gene silencing. Herein, we show that HP1γ interacts with breast cancer type 1 susceptibility protein (BRCA1) and regulates BRCA1-mediated transcription via modulation of promoter occupancy and histone modification. We used several HP1γ mutants and small interfering RNAs for histone methyltransferases to show that BRCA1-HP1γ interaction, but not methylated histone binding, is important in HP1γ repression of BRCA1-mediated transc ...[more]

PMID: 23074186

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Dataset Information

Suppression and recovery of BRCA1-mediated transcription by HP1? via modulation of promoter occupancy.

Publications

Suppression and recovery of BRCA1-mediated transcription by HP1γ via modulation of promoter occupancy.

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