biostudies-literatureUnknown42(11)Calderon MRCanadian Institutes of Health ResearchWe identified a novel interaction between ligand-dependent corepressor (LCoR) and the corepressor KRAB-associated protein-1 (KAP-1). The two form a complex with C2H2 zinc-finger transcription factor ZBRK1 on an intronic binding site in the growth arrest and DNA-damage-inducible α (GADD45A) gene and a novel site in the fibroblast growth factor 2 (FGF2) gene. Chromatin at both sites is enriched for histone methyltransferase SETDB1 and histone 3 lysine 9 trimethylation, a repressive epigenetic mark. Depletion of ZBRK1, KAP-1 or LCoR led to elevated GADD45A and FGF2 expression in malignant and non-malignant breast epithelial cells, and caused apoptotic death. Loss of viability could be rescued by simultaneous knockdowns of FGF2 and transcriptional coregulators or by blocking FGF2 function. FGFNucleic acids research7012-27https://www.ebi.ac.uk/biostudies/studies/S-EPMC4066800biostudies-literatureLigand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.PMC4066800Dimitrov VVerway MMader SWhite JHBouttier MCalderon MRBenslama ROBirlea MfalseLigand-dependent corepressor contributes to transcriptional repression by C2H2 zinc-finger transcription factor ZBRK1 through association with KRAB-associated protein-1.We identified a novel interaction between ligand-dependent corepressor (LCoR) and the corepressor KRAB-associated protein-1 (KAP-1). The two form a complex with C2H2 zinc-finger transcription factor ZBRK1 on an intronic binding site in the growth arrest and DNA-damage-inducible α (GADD45A) gene and a novel site in the fibroblast growth factor 2 (FGF2) gene. Chromatin at both sites is enriched for histone methyltransferase SETDB1 and histone 3 lysine 9 trimethylation, a repressive epigenetic mark. Depletion of ZBRK1, KAP-1 or LCoR led to elevated GADD45A and FGF2 expression in malignant and non-malignant breast epithelial cells, and caused apoptotic death. Loss of viability could be rescued by simultaneous knockdowns of FGF2 and transcriptional coregulators or by blocking FGF2 function. FGF2014-01-01T00:00:00Z2014 Jun2025-04-21T20:09:36.575Z2019-03-27T01:30:40ZS-EPMC40668002482945910.1093/nar/gku413