{"doi":"10.1101/2022.12.15.520587","title":"A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin","abstract":"Summary Plasticity between cell lineages is a fundamental but poorly understood property of regenerative tissues. In the gut tube, small intestine absorbs nutrients whereas colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screen, we identified MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrain colonic plasticity. MTA2 loss in adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-binds with HNF4A, an activating pan-intestine transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic and gain on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through a HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages; their release unleashes plasticity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":314075,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":649379,"name":"Xiaofeng Huang","orcid":"0000-0001-8571-4667","position":1,"is_corresponding":false},{"id":649380,"name":"Pratik Singh","orcid":"0000-0001-6830-2177","position":2,"is_corresponding":false},{"id":649382,"name":"Ying Lan","orcid":"0000-0001-7778-5414","position":3,"is_corresponding":false},{"id":239237,"name":"Jesús M. Gómez-Salinero","orcid":null,"position":4,"is_corresponding":false},{"id":237950,"name":"Shahin Rafii","orcid":"0000-0001-5605-1067","position":5,"is_corresponding":false},{"id":1013007,"name":"Mike Verzi","orcid":null,"position":6,"is_corresponding":false},{"id":71354,"name":"Ramesh A. Shivdasani","orcid":"0000-0002-2828-1727","position":7,"is_corresponding":false},{"id":237947,"name":"Qiao Zhou","orcid":"0000-0002-0099-3909","position":8,"is_corresponding":false},{"id":649377,"name":"Wei Yong Gu","orcid":"0000-0002-5958-2653","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T00:33:48.490749Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}