GATA zinc finger domain-containing protein 2A (GATAD2A)

GATA zinc finger domain-containing protein 2A (GATAD2A), also known as p66alpha, is a fundamental subunit of the Nucleosome Remodeling and Deacetylase (NuRD) complex, which integrates ATP-dependent chromatin remodeling and histone deacetylase activities [UniProt Q86YP4]. It functions primarily as a transcriptional repressor by facilitating the assembly and recruitment of the NuRD complex to specific genomic loci, often those marked by DNA methylation [PubMed 22492555]. GATAD2A contains a conserved GATA-type zinc finger and a CR2 domain that are essential for its interaction with other complex members like MBD2 and HDAC1/2 [NCBI Gene 54815]. In human health, GATAD2A is implicated in various cancers, where its overexpression is linked to the silencing of tumor suppressor genes and promoted metastasis [PubMed 28633017]. It also plays a role in maintaining stem cell pluripotency and directing lineage commitment during embryonic development [PubMed 23934157]. Although there are currently no clinical drugs that specifically target GATAD2A directly, it is considered a high-interest target for epigenetic therapy due to its central role in the NuRD complex's stability and function [PubMed 30122353]. Inhibiting GATAD2A could potentially reactivate silenced genes in cancer cells, offering a therapeutic strategy similar to existing HDAC inhibitors but with potentially higher specificity [PubMed 31435058].

Other names

p66alphap66aTranscriptional repressor p66-alpha

GATAD2A acts as a critical scaffold within the Nucleosome Remodeling and Deacetylase (NuRD) complex, facilitating the recruitment of the complex to methylated DNA and mediating transcriptional repression through histone deacetylation and ATP-dependent chromatin remodeling [PubMed 11739395, UniProt Q86YP4].