{"doi":"10.1016/j.jbc.2022.102578","title":"Transcription suppression is mediated by the HDAC1–Sin3 complex in Xenopus nucleoplasmic extract","abstract":"Modification of histones provides a dynamic mechanism to regulate chromatin structure and access to DNA. Histone acetylation, in particular, plays a prominent role in controlling the interaction between DNA, histones, and other chromatin-associated proteins. Defects in histone acetylation patterns interfere with normal gene expression and underlie a wide range of human diseases. Here, we utilize Xenopus egg extracts to investigate how changes in histone acetylation influence transcription of a defined gene construct. We show that inhibition of histone deacetylase 1 and 2 (HDAC1/2) specifically counteracts transcription suppression by preventing chromatin compaction and deacetylation of histone residues H4K5 and H4K8. Acetylation of these sites supports binding of the chromatin reader and transcription regulator BRD4. We also identify HDAC1 as the primary driver of transcription suppression and show that this activity is mediated through the Sin3 histone deacetylase complex. These findings highlight functional differences between HDAC1 and HDAC2, which are often considered to be functionally redundant, and provide additional molecular context for their activity. Modification of histones provides a dynamic mechanism to regulate chromatin structure and access to DNA. Histone acetylation, in particular, plays a prominent role in controlling the interaction between DNA, histones, and other chromatin-associated proteins. Defects in histone acetylation patterns interfere with normal gene expression and underlie a wide range of human diseases. Here, we utilize Xenopus egg extracts to investigate how changes in histone acetylation influence transcription of a defined gene construct. We show that inhibition of histone deacetylase 1 and 2 (HDAC1/2) specifically counteracts transcription suppression by preventing chromatin compaction and deacetylation of histone residues H4K5 and H4K8. Acetylation of these sites supports binding of the chromatin reader and transcription regulator BRD4. We also identify HDAC1 as the primary driver of transcription suppression and show that this activity is mediated through the Sin3 histone deacetylase complex. These findings highlight functional differences between HDAC1 and HDAC2, which are often considered to be functionally redundant, and provide additional molecular context for their activity. The eukaryotic genome is bound by highly conserved proteins called histones, which are essential for the organization and compaction of genetic material within the nucleus (1Mariño-Ramírez L. Kann M.G. Shoemaker B.A. Landsman D. Histone structure and nucleosome stability.Expert Rev. Proteomics. 2005; 2: 719-729Crossref PubMed Scopus (205) Google Scholar). The core histone is an octamer (comprised of two copies of H2A, H2B, H3, and H4) that is wrapped by ∼147 bp of DNA to form a nucleosome (2Kornberg R.D. Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome.Cell. 1999; 98: 285-294Abstract Full Text Full Text PDF PubMed Scopus (1459) Google Scholar). Nucleosomes form the basic building block of chromatin, which includes interactions between DNA, RNA, and protein. Additional linker histones and histone variants also play important roles in the formation and regulation of chromatin structure (3Hergeth S.P. Schneider R. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.EMBO Rep. 2015; 16: 1439-1453Crossref PubMed Scopus (217) Google Scholar, 4Quénet D. Histone variants and disease.Int. Rev. Cell Mol. Biol. 2018; 335: 1-39Crossref PubMed Scopus (11) Google Scholar). Cells control access to DNA by regulating the compaction and decompaction of chromatin (5Allis C.D. Jenuwein T. The molecular hallmarks of epigenetic control.Nat. Rev. Genet. 2016; 17: 487-500Crossref PubMed Scopus (1503) Google Scholar). These dynamic changes in chromatin structure are critical for normal gene expression profiles and cell cycle progression (6Ma Y. Kanakousaki K. ","journal":"Journal of Biological Chemistry","year":2022,"id":275814,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":717464,"name":"Baicheng Lin","orcid":null,"position":1,"is_corresponding":false},{"id":733917,"name":"David T. Long","orcid":"0000-0001-9232-0316","position":2,"is_corresponding":false},{"id":863129,"name":"Colleen E. Quaas","orcid":"0000-0002-7853-3128","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T00:28:21.971703Z","pmid":"36220390","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":[]}