GeneID: 371

Description:
This gene encodes a member of the CHD family of proteins (ATP-dependent chromatin remodelers) which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD4 is a key component of NuRD, a protein complex that comprises both nucleosome remodeling and deacetylase activities. The NuRD complex has been associated with epigenetic mechanisms of transcriptional repression during development, and has been shown to play an important role in globin regulation. Κnockdown of the CHD4 protein led to an increase in embryonic and fetal globin gene expression in human adult erythroid cells. The effect of CHD4 on γ-globin gene silencing appears to be mediated both through the MBD2-NuRD repressor complex and through positive regulation of the KLF1 and BCL11A genes. CRISPR screening in human adult erythroid precursors identified CHD4 as a candidate repressor of γ-globin gene expression, while the CHD4 CHDCT2 domain is critical for NuRD complex assembly. CHD4 is a potential target for HbF induction in β-haemoglobinopathies.

Synonyms: CHD-4 , Mi-2b , SIHIWES , Mi2-BETA

Comments:
N/A

Number of entries/variants: 0

1. Thein SL, Genetic association studies in β-hemoglobinopathies., Hematology Am Soc Hematol Educ Program, 2013(0), 354-61, 2013 PubMed
2. Amaya M, Desai M, Gnanapragasam MN, Wang SZ, Zu Zhu S, Williams DC, Ginder GD, Mi2β-mediated silencing of the fetal γ-globin gene in adult erythroid cells., Blood, 121(17), 3493-501, 2013 PubMed
3. Hoffmeister H, Fuchs A, Erdel F, Pinz S, Gröbner-Ferreira R, Bruckmann A, Deutzmann R, Schwartz U, Maldonado R, Huber C, Dendorfer AS, Rippe K, Längst G, CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality., Nucleic Acids Res., 45(18), 10534-10554, 2017 PubMed
4. Sher F, Hossain M, Seruggia D, Schoonenberg VAC, Yao Q, Cifani P, Dassama LMK, Cole MA, Ren C, Vinjamur DS, Macias-Trevino C, Luk K, McGuckin C, Schupp PG, Canver MC, Kurita R, Nakamura Y, Fujiwara Y, Wolfe SA, Pinello L, Maeda T, Kentsis A, Orkin SH, Bauer DE, Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis., Nat Genet, 51(7), 1149-1159, 2019 PubMed