CoREST-associated histone deacetylase complex (CoREST-HDAC complex)

The **CoREST-associated histone deacetylase complex** is a multiprotein enzymatic complex that includes HDAC1 and/or HDAC2 (class I histone deacetylases), the transcriptional corepressor CoREST (RCOR1), and other partners such as LSD1 (also known as KDM1A, a lysine demethylase)[1][2][3][4]. This complex plays a pivotal role in chromatin remodeling and transcriptional repression by catalyzing the removal of acetyl and crotonyl groups from specific lysine residues on histone tails, thus promoting chromatin compaction and gene silencing[3][4][5]. The CoREST-HDAC complex is particularly crucial for repressing neuronal genes in non-neuronal cells and has been implicated in various physiological and pathological contexts, including cancer and neurological disorders[4][7]. Several small-molecule inhibitors have been developed to selectively target the HDACs within the CoREST complex, with the aim of modulating gene expression in disease without the broad toxicity of pan-HDAC inhibitors[4][6]. Dual inhibitors (such as corin) can engage both HDAC1/2 and LSD1 active sites, representing a novel strategy for sustained and selective transcriptional reactivation of specific gene sets[2]. Safety concerns primarily revolve around systemic toxicities, such as cytopenias, but newer complex-selective agents show promise for reducing side effects by sparing other cellular HDAC functions[4][6].

Other names

CoREST complexHDAC–CoREST co-repressor complexCoREST-HDAC complex

Inhibition of HDAC enzymatic activity within the CoREST complex; Dual inhibition of HDAC1 and LSD1 enzymatic activities; Transcriptional derepression of neural or tumor suppressor genes