{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["121(23)"],"submitter":["Mondal A"],"pubmed_abstract":["Critical lineage commitment events are staged by multiple transcription factors (TFs) binding to their cognate motifs, often positioned at nucleosome-enriched regions of chromatin. The underlying mechanism remains elusive due to difficulty in disentangling the heterogeneity in chromatin states. Using a novel coarse-grained model and molecular dynamics simulations, here we probe the association of Sox2 and Oct4 proteins that show clustered binding at the entry-exit region of a nucleosome. The model captures the conformational heterogeneity of nucleosome breathing dynamics that features repeated wrap-unwrap transitions of a DNA segment from one end of the nucleosome. During the dynamics, DNA forms bulges that diffuse stochastically and may regulate the target search dynamics of a protein by nonspecifically interacting with it. The overall search kinetics of the TF pair follows a \"dissociation-compensated-association\" mechanism, where Oct4 binding is facilitated by the association of Sox2. The cooperativity stems from a change in entropy caused by an alteration in the nucleosome dynamics upon TF binding. The binding pattern is consistent with a live-cell single-particle tracking experiment, suggesting the mechanism observed for clustered binding of a TF pair, which is a hallmark of cis-regulatory elements, has broader implications in understanding gene regulation in a complex chromatin environment."],"journal":["Biophysical journal"],"pagination":["4526-4542"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9748375"],"repository":["biostudies-literature"],"pubmed_title":["Nucleosome breathing facilitates cooperative binding of pluripotency factors Sox2 and Oct4 to DNA."],"pmcid":["PMC9748375"],"pubmed_authors":["Mishra SK","Mondal A","Bhattacherjee A"],"additional_accession":[]},"is_claimable":false,"name":"Nucleosome breathing facilitates cooperative binding of pluripotency factors Sox2 and Oct4 to DNA.","description":"Critical lineage commitment events are staged by multiple transcription factors (TFs) binding to their cognate motifs, often positioned at nucleosome-enriched regions of chromatin. The underlying mechanism remains elusive due to difficulty in disentangling the heterogeneity in chromatin states. Using a novel coarse-grained model and molecular dynamics simulations, here we probe the association of Sox2 and Oct4 proteins that show clustered binding at the entry-exit region of a nucleosome. The model captures the conformational heterogeneity of nucleosome breathing dynamics that features repeated wrap-unwrap transitions of a DNA segment from one end of the nucleosome. During the dynamics, DNA forms bulges that diffuse stochastically and may regulate the target search dynamics of a protein by nonspecifically interacting with it. The overall search kinetics of the TF pair follows a \"dissociation-compensated-association\" mechanism, where Oct4 binding is facilitated by the association of Sox2. The cooperativity stems from a change in entropy caused by an alteration in the nucleosome dynamics upon TF binding. The binding pattern is consistent with a live-cell single-particle tracking experiment, suggesting the mechanism observed for clustered binding of a TF pair, which is a hallmark of cis-regulatory elements, has broader implications in understanding gene regulation in a complex chromatin environment.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-28T01:35:31.688Z","creation":"2025-04-05T22:24:26.501Z"},"accession":"S-EPMC9748375","cross_references":{"pubmed":["36321206"],"doi":["10.1016/j.bpj.2022.10.039"]}}