HDAC7 (histone deacetylase 7; HGNC:14067, NCBI Gene ID 51564) is a human locus mapped to chromosome band 12q13.11 that encodes class IIa signal-responsive nucleocytoplasmic shuttle protein HDAC7 (952 aa; 103 kDa). HDAC7 acts in endothelial MEF2 repression of MMP10 (vascular wall stability) & thymocyte Nur77 (NR4A1) repression during T-cell negative selection, together with HDAC4 (Class IIa Paralog Gene), HDAC5 (Class IIa Paralog Gene), and HDAC9 (Class IIa Paralog Gene). Encodes Class IIa histone deacetylase 7, required for vascular endothelial integrity and thymocyte negative selection.
Approved Symbol
HDAC7
Chromosomal Locus
12q13.11
Encoded Product
Class IIa signal-responsive nucleocytoplasmic shuttle protein HDAC7 (952 aa; 103 kDa)
Primary Pathway
Endothelial MEF2 repression of MMP10 (vascular wall stability) & thymocyte Nur77 (NR4A1) repression during T-cell negative selection
Genomic Organization & Cytogenetic Locus: 28-exon gene on chromosome 12q13.11 encoding a 952-amino-acid Class IIa protein with an N-terminal MEF2-binding motif, four 14-3-3 phosphorylation sites (phosphorylated by PKD, CaMK, and SIK kinases), and a C-terminal His-substituted pseudo-deacetylase domain that recruits the NCoR1/SMRT-HDAC3 complex.
Cellular & Tissue Expression Profile: Specifically enriched in vascular endothelial cells during blood-vessel morphogenesis, CD4+CD8+ double-positive cortical thymocytes in the thymus, osteoblasts, and inflammatory macrophages.
Molecular Function & Pathways
Biochemical & Physiological Mechanism: In vascular endothelial cells, nuclear HDAC7 binds MEF2 transcription factors to repress matrix metalloproteinase-10 (MMP10); if HDAC7 is lost, unrestrained MMP10 degrades the perivascular extracellular matrix and causes lethal embryonic vascular rupture; in CD4+CD8+ double-positive thymocytes, nuclear HDAC7 represses the pro-apoptotic orphan nuclear receptor Nur77 (NR4A1) until strong T-cell receptor engagement activates Protein Kinase D (PKD) to phosphorylate and export HDAC7 into the cytoplasm—derepressing Nur77 to eliminate self-reactive T cells during negative selection.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Homozygous deletion of Hdac7 in mice is embryonically lethal at day 11.0 due to loss of endothelial cell-cell adhesion, vessel dilatation, and hemorrhage; in human B-cell precursor acute lymphoblastic leukemia, loss of HDAC7 fails to repress MYC and correlates with poor prognosis.
Therapeutic & Clinical Pharmacology: In pro-inflammatory M1 macrophages, cytoplasmic HDAC7 interacts with pyruvate kinase M2 (PKM2) to amplify LPS-induced HIF-1alpha (HIF1A) and IL-1beta transcription, making Class IIa HDAC7 blockade a target in chronic inflammatory disease.