Histone deacetylase 1 within the CoREST complex (HDAC1-CoREST complex)

Histone deacetylase 1 (HDAC1) within the CoREST complex is a multi-protein epigenetic regulator consisting of the catalytic subunit HDAC1, the scaffolding protein REST corepressor 1 (RCOR1/CoREST), and the lysine-specific demethylase 1 (LSD1/KDM1A) [4, 10, 15]. This complex plays a pivotal role in silencing neuronal genes and regulating synaptic plasticity, making it a key target for treating neurodegenerative diseases like Alzheimer's [1, 2, 3]. In oncology, the complex is involved in maintaining the undifferentiated state of cancer cells and suppressing tumor suppressor genes in malignancies such as melanoma and leukemia [4, 10, 17]. Selective inhibitors, such as the Rodin series, target the HDAC activity specifically within the CoREST environment to improve safety profiles by reducing the hematological side effects typically associated with pan-HDAC inhibitors [1, 2]. Dual-action inhibitors like Corin target both the HDAC and LSD1 components of the complex to achieve synergistic anti-tumor effects [4, 11]. Overall, the HDAC1-CoREST complex serves as a critical node for integrating histone deacetylation and demethylation to control gene expression programs in health and disease [13, 15].

Other names

HDAC1-RCOR1 complexHDAC1-LSD1-CoREST complexCoREST-HDAC1 complexRCOR1-HDAC1 complex

Inhibition of the catalytic activity of HDAC1 specifically when associated with the CoREST complex, leading to increased acetylation of histones (e.g., H3K9) and non-histone proteins, which restores the expression of silenced genes involved in synaptic function or tumor suppression.