CHD chromatin remodelers

CHD proteins are grouped into three subfamilies based on their other domains and mode of action.

Human CHD1 and CHD2, neither of which is very well studied, are part of Subfamily I. Members of this family have an N-terminal DNA binding region that preferentially interacts with AT-rich DNA. Based on studies in S. cerevisiae, which has a single CHD protein, CHD1, subfamily 1 members appear to function as monomeric or dimeric ATPases, and may additionally interact with CHD2 (Tran et al, 2000; Luijsterburg et al, 2016; reviewed in Marfella and Imbalzano, 2007; Alendar and Berns, 2021). Human CHD1 has been shown to bind to H3K4 marks and may function in transcriptional activation.

Human CHD3, CHD4 and CHD5 are part of Subfamily II and are characterized by the presence of two plant homeodomains (PHD), zinc finger-like domains that have been shown to bind to trimethylated histones. CHD3, 4 and 5 all participate as the ATPase component of distinct NuRD (nucleosome remodeling deacetylase) complexes that couple ATP-dependent nucleosome remodeling with histone deacetylase activity (Hoffmeister et al, 2017; Kolla et al, 2015; Miccio et al, 2010; reviewed in Alendar and Berns 2021; Boulasiki et al, 2023; Eusterman et al, 2024; Asmamaw et al, 2024).

Human CHD6, CHD7, CHD8 and CHD9 are part of Subfamily III and are orthologs of the Drosophila Kismet enzyme. Subfamily III CHD proteins are characterized by the presence of SANT and BRK (Brahma Kismet) domains, both commonly found in proteins involved in histone binding and chromatin remodeling (reviewed in Mills, 2017; Alendar and Berns, 2021). Human Subfamily III members have been shown to act as both transcriptional co-activators and co-repressors (reviewed in Mills, 2017; Alendar and Berns, 2021; Zhang et al, 2024).