Histone deacetylase 1

Histone Deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene. HDAC1 belongs to the class I of the histone deacetylase family, a group of enzymes that play a crucial role in modifying chromatin structure and regulating gene expression by removing acetyl groups from histone proteins. This action leads to the condensation of chromatin structure and suppression of gene transcription, making HDAC1 a key player in cell cycle regulation, cell proliferation, and differentiation.

Function

HDAC1 is involved in the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3, and H4). This process is critical for the regulation of transcription, DNA repair, cell cycle progression, and developmental events. HDAC1 forms complexes with other proteins, such as mSin3A, NuRD, and CoREST, which are essential for targeting the enzyme to specific genes and for the repression of transcription.

Clinical Significance

HDAC1 has been implicated in a variety of human diseases, including cancer, neurological disorders, and cardiovascular diseases. Its overexpression or deregulated activity is associated with the silencing of tumor suppressor genes and the activation of oncogenes, contributing to the progression of cancer. Inhibitors of HDAC1 are being explored as therapeutic agents in cancer treatment, as they can induce cell cycle arrest, apoptosis, and differentiation in cancer cells.

Structure

The HDAC1 protein contains a deacetylase domain that is highly conserved among the class I HDAC family. This domain is responsible for its enzymatic activity of removing acetyl groups from histones. HDAC1 also has sequences that mediate interactions with co-repressors and other proteins, facilitating its recruitment to specific genomic loci.

Interaction

HDAC1 interacts with a variety of proteins, including transcription factors, co-repressors, and other histone modifying enzymes. These interactions are crucial for the regulation of gene expression and the maintenance of chromatin structure. For example, the interaction with mSin3A and NuRD complexes is important for the repression of genes involved in cell cycle regulation and differentiation.

Inhibitors

HDAC1 inhibitors are a class of compounds that block the activity of HDAC1, leading to increased acetylation of histones and activation of gene expression. These inhibitors are being studied for their potential use in cancer therapy, as they can induce apoptosis and inhibit the proliferation of cancer cells. Examples of HDAC1 inhibitors include trichostatin A and vorinostat.

See Also

• Histone deacetylase
• Epigenetics
• Gene expression
• Cancer therapy