{"doi":"10.17615/85rh-wy88","title":"A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing","abstract":"Immune cells develop endotoxin tolerance (ET) after prolonged stimulation. ET increases the level of a repression mark H3K9me2 in the transcriptional-silent chromatin specifically associated with pro-inflammatory genes. However, it is not clear what proteins are functionally involved in this process. Here we show that a novel chromatin activity based chemoproteomic (ChaC) approach can dissect the functional chromatin protein complexes that regulate ET-associated inflammation. Using UNC0638 that binds the enzymatically active H3K9-specific methyltransferase G9a/GLP, ChaC reveals that G9a is constitutively active at a G9a-dependent mega-dalton repressome in primary endotoxin-tolerant macrophages. G9a/GLP broadly impacts the ET-specific reprogramming of the histone code landscape, chromatin remodeling, and the activities of select transcription factors. We discover that the G9a-dependent epigenetic environment promotes the transcriptional repression activity of c-Myc for gene-specific co-regulation of chronic inflammation. ChaC may be also applicable to dissect other functional protein complexes in the context of phenotypic chromatin architectures.","journal":"UNC Libraries","year":2020,"id":113872,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11782,"name":"Yanbao Yu","orcid":"0000-0003-2994-1974","position":1,"is_corresponding":false},{"id":536618,"name":"Zhou Li","orcid":"0000-0002-7977-3692","position":2,"is_corresponding":false},{"id":536619,"name":"Xian Chen","orcid":"0000-0003-4301-1909","position":3,"is_corresponding":false},{"id":443719,"name":"Jian Jin","orcid":"0000-0001-8586-0429","position":4,"is_corresponding":false},{"id":536620,"name":"Feng Liu","orcid":"0000-0002-7589-2264","position":5,"is_corresponding":false},{"id":536621,"name":"Cui Liu","orcid":"0000-0001-6724-3881","position":6,"is_corresponding":false},{"id":11802,"name":"Harsha P. Gunawardena","orcid":"0000-0003-3245-3293","position":7,"is_corresponding":false},{"id":11808,"name":"John A. Wrobel","orcid":"0000-0002-5828-9359","position":8,"is_corresponding":false},{"id":536617,"name":"Xin Wei","orcid":"0000-0002-9720-6771","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:25.964732Z","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":[]}