HDAC2

HDAC2 is a member of the histone deacetylase family, specifically class I, and is a zinc-dependent enzyme that localizes primarily to the nucleus. It catalyzes the removal of acetyl groups from lysine residues on histone tails, notably H3 and H4, promoting chromatin compaction and transcriptional repression.

In cells, HDAC2 functions as part of multiprotein corepressor complexes such as Sin3A, NuRD, NCoR, and CoREST, enabling targeted deacetylation of specific gene loci. Through these interactions, HDAC2 regulates gene expression programs essential for development, neuronal differentiation, synaptic plasticity, and memory formation.

HDAC2 expression is widespread but enriched in brain, heart, and other tissues, and its activity is modulated by signaling pathways, post-translational modifications, and interacting partners. Dysregulation of HDAC2 has been linked to various conditions. In the nervous system, elevated HDAC2 can repress synaptic plasticity genes and impair learning and memory, whereas reduced HDAC2 activity can enhance cognitive function in some models. In cancer, HDAC2 can contribute to transcriptional silencing of tumor suppressor genes and influence cell proliferation and survival, and HDAC inhibitors are used clinically to treat certain malignancies. HDAC2 is also investigated in neurodegenerative diseases and inflammatory conditions, where aberrant deacetylation may affect neuronal resilience and immune signaling.

Therapeutically, broad-spectrum and selective HDAC inhibitors target class I enzymes, including HDAC2, with approved agents used in oncology and ongoing research for neuropsychiatric indications. Ongoing work seeks to delineate isoform-specific roles and develop selective modulators to maximize efficacy while limiting adverse effects.