HDAC1 (Histone Deacetylase 1 Class I Nuclear Corepressor Complex Catalytic Core Gene)
HDAC1 (histone deacetylase 1; HGNC:4852, NCBI Gene ID 3065) is a human locus mapped to chromosome band 1p35.2-p35.1 that encodes zn2+-dependent Class I nuclear histone deacetylase 1 (482 aa; 55 kDa; EC 3.5.1.98). HDAC1 acts in catalytic subunit of Sin3A, NuRD, CoREST & MiDAC chromatin corepressor complexes; recruited by RB1 to silence E2F & CDKN1A, together with HDAC2 (83%-Identical Class I Paralog in Sin3/NuRD/CoREST), HDAC3 (Class I NCoR/SMRT Deacetylase Gene), and RB1 (Recruits HDAC1 to Repress E2F S-Phase Promoters). Encodes the archetype Class I zinc-dependent nuclear histone deacetylase that forms the catalytic core of the Sin3, NuRD, and CoREST chromatin-remodeling complexes.
Approved Symbol
HDAC1
Chromosomal Locus
1p35.2-p35.1
Encoded Product
Zn2+-dependent Class I nuclear histone deacetylase 1 (482 aa; 55 kDa; EC 3.5.1.98)
Primary Pathway
Catalytic subunit of Sin3A, NuRD, CoREST & MiDAC chromatin corepressor complexes; recruited by RB1 to silence E2F & CDKN1A
Clinical / Therapeutic Role
Target of FDA-approved HDAC inhibitors (vorinostat, romidepsin, entinostat, tucidinostat) in T-cell lymphomas & breast cancer
Gene Structure & Expression
Genomic Organization & Cytogenetic Locus: 14-exon gene on chromosome 1p35.2-p35.1 (derived from an ancient duplication with HDAC2, sharing 83% amino-acid identity) encoding a 482-amino-acid enzyme with a conserved arginase-like alpha/beta deacetylase fold containing a deep 11-angstrom hydrophobic tubular channel that positions a catalytic Zn2+ ion and two His-Asp charge-relay dyads, plus a C-terminal disordered tail phosphorylated by casein kinase II (CK2 at Ser421/Ser423) to trigger complex assembly.
Cellular & Tissue Expression Profile: Ubiquitously expressed at high levels in the nucleus of all proliferating embryonic stem cells, hematopoietic progenitors, and somatic cells.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Requires incorporation into multiprotein complexes containing ELM2-SANT or InsP6 (inositol hexakisphosphate)-binding subunits for maximal enzymatic activity: inside the Sin3A/B, NuRD (CHD4-MTA1/2), CoREST (RCOR1-LSD1), and mitotic MiDAC complexes, HDAC1 hydrolyzes epsilon-N-acetyl-L-lysine amide bonds on Histone H3 (H3K9ac, H3K14ac, H3K27ac) and Histone H4—restoring the positive +1 charge of lysine tails so they tighten electrostatically around negatively charged DNA and silence transcription of E2F target genes (when recruited by RB1) and p21 (CDKN1A).
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Unlike any other individual Class I or II HDAC, germline homozygous deletion of Hdac1 is early embryonically lethal around day 9.5 due to severe proliferation defects and unrestrained p21/p27 expression; in adult neurons, HDAC1 also interacts with FUS and SIRT1 to promote DNA double-strand break repair.
Therapeutic & Clinical Pharmacology: Direct catalytic target of hydroxamic acid pan-HDAC inhibitors (vorinostat / SAHA, belinostat, panobinostat) and Class-I-selective bicyclic peptide (romidepsin) and benzamide inhibitors (entinostat, tucidinostat / chidamide), which chelate the active-site Zn2+ ion to hyperacetylate histones, derepress CDKN1A (p21), and induce tumor cell-cycle arrest and apoptosis.