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In our study, we describe how, during castration or AR inhibition, HES6 overexpression can modulate the AR regulome, maintaining chromatin binding at a proportion of ARBS in the absence of hormone stimulation.
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This evidently requires some mechanism for maintaining chromatin integrity.
In this study, we report that HES6 maintains AR chromatin binding at a critical subset of sites, which are enriched for cell cycle regulatory genes under the control of E2F1, induces resistance to anti-androgens and castration and predicts poor outcome in the clinical setting.
Nuclear matrix and matrix binding proteins maintain chromatin architecture that is altered in cancer [1].
In contrast, once the repressive chromatin state at the promoter is established, it is self-maintained in the absence of an inducing signal due to initial modification, providing new binding sites for the enzymes that maintain chromatin modifications.
These results show that the observed decondensation defects correlate with persistent chromatin binding of condensin I. To test whether condensin is required to maintain chromatin condensation when the initiation of replication is blocked, we performed double depletions of mcm-7 and smc-4, or cdc-45 and smc-4, in embryos expressing GFP-CAPG-1 and mCherry-H2B.
CCCTC-binding factor (CTCF), a ubiquitously expressed and evolutionarily conserved 11-zinc-finger DNA binding protein, is intimately involved in gene regulation, helping to establish and maintain chromatin architecture and long-range DNA interactions.
Smolle, M. et al. Chromatin remodelers Isw1 and Chd1 maintain chromatin structure during transcription by preventing histone exchange.
Grande, M. et al. Crosstalk between Nap1 protein and Cds1 checkpoint kinase to maintain chromatin integrity.
Smolle et al. review two recent papers that show how the Set2-mediated methylation of H3K36 maintains chromatin structure by limiting histone dynamics over gene bodies, either by recruiting chromatin remodelers that preserve ordered nucleosomal distribution or by lowering the binding affinity of histone chaperones for histones, preventing their removal.
We also identified the landscape of PARP1-mRNA binding sites8,9, placing PARP1 in the group of chromatin binding proteins that also bind RNA.
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