Class I histone deacetylase (HDAC) (Class I HDAC)

Class I histone deacetylases (HDACs), which include the isoforms HDAC1, HDAC2, HDAC3, and HDAC8, are nuclear enzymes that play a pivotal role in the epigenetic regulation of gene expression by removing acetyl groups from histone tails (UniProt). This deacetylation promotes a condensed chromatin structure, leading to the transcriptional silencing of genes involved in cell cycle control and tumor suppression. In the specific context of Epstein-Barr virus (EBV)-positive lymphoid cells, Class I HDACs are recruited to viral promoters, such as the BZLF1 promoter, to maintain the virus in a latent state and evade immune detection (PubMed: 15140983). Therapeutic targeting of these enzymes with HDAC inhibitors (HDACis) disrupts this silencing, inducing the viral lytic cycle—a strategy known as lytic induction therapy or 'shock and kill' (PubMed: 21835908). This reactivation forces the expression of viral antigens and enzymes, making the infected lymphoid cells susceptible to antiviral prodrugs like ganciclovir and host immune responses. Consequently, Class I HDACs are significant targets in treating EBV-associated malignancies, where they simultaneously drive oncogenic gene expression patterns and facilitate viral persistence.

Other names

HDAC1HDAC2HDAC3HDAC8RPD3-like histone deacetylaseHistone deacetylase class I

Inhibition of the enzymatic removal of acetyl groups from lysine residues on histone tails, leading to hyperacetylation, chromatin relaxation, and the reactivation of silenced genes, including EBV lytic genes.