Histone deacetylase-corepressor for element-1-silencing transcription factor complex (HDAC-CoREST complex) (HDAC-CoREST)

The Histone deacetylase-corepressor for element-1-silencing transcription factor complex (HDAC-CoREST complex) is a multi-protein epigenetic assembly that functions as a key transcriptional corepressor. It typically consists of the enzymes Histone deacetylase 1 (HDAC1) or Histone deacetylase 2 (HDAC2), the scaffold protein RE1-silencing transcription factor corepressor 1 (RCOR1/CoREST), and the lysine-specific demethylase 1 (LSD1/KDM1A) (PubMed: 15601816). This complex is unique because it couples two distinct enzymatic activities—deacetylation and demethylation—to coordinately remove activating histone marks, leading to chromatin condensation and gene silencing (UniProt: Q9UKL0). Biologically, it is essential for maintaining the repression of neuronal genes in non-neuronal tissues and regulating the differentiation of hematopoietic stem cells (PubMed: 20547104). In disease contexts, the complex is frequently hijacked; for instance, in acute myeloid leukemia (AML), it suppresses genes required for myeloid differentiation, while in Alzheimer's disease, its aberrant activity contributes to cognitive decline (PubMed: 30108115). Therapeutic strategies focus on small-molecule inhibitors, such as dual HDAC/LSD1 inhibitors like Corin, which aim to disrupt the complex's repressive function and restore the expression of silenced tumor-suppressor or differentiation genes (PubMed: 29438698).

Other names

CoREST complexRCOR1-HDAC complexLSD1-CoREST-HDAC complexREST corepressor complex

Dual inhibition of histone deacetylase (HDAC) and lysine-specific demethylase 1 (LSD1) activities within the complex to reverse epigenetic silencing of target genes (PubMed: 29438698).