Reactome | NuRD complex assembly

NuRD complex assembly

Stable Identifier

R-HSA-9937850

Type

Pathway

Species

Homo sapiens

ReviewStatus

3/5

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The nucleosome remodeling and deacetylase (NuRD) complex is a multi-protein ATP-dependent chromatin remodeler that, uniquely, combines histone deacetylase activity with ATPase and DNA translocase activities (Tong et al, 1998; Xue et al, 1998; reviewed in Alendar and Berns, 2021; Boulasiki et al, 2023; Eustermann et al, 2024). In humans, the ATPase activity is provided by one of three CHD proteins, CHD3, CHD4 or CHD5, each of which assemble into NuRD complexes with overlapping but distinct composition and roles (Le Guezennec et al, 2006; Kolla et al, 2015; Nitarska et al, 2016; reviewed in Alendar and Berns, 2021; Asmamaw et al, 2024). Histone deacetylase activity is contributed by either HDAC1 or HDAC2 (Zhang et al, 1999). In addition, the NuRD complex contains five additional core components, each of which exists in humans as members of paralogous protein families: metastasis-associated protein 1 (MTA1), MTA2 or MTA3; RBBP4 or RBBP7; methyl-CpG-binding domain protein 2 (MBD2) or MBD3; GATAD2A or GATAD2B; and cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) or CDK2AP2 (reviewed in Alendar and Berns, 2021; Boulasiki et al, 2023; Asmamaw et al, 2024). NuRD complex assembly is thought to nucleate around a core complex consisting of HDAC1/2, MTA1/2/3 and RBBP4/7, to which the other subunits are then recruited (reviewed in Boulasiki et al, 2023; Asmamaw et al, 2024). The compositional diversity of NuRD complexes has made categorically defining complex stoichiometry and structure challenging, so although numerous structures of individual components or subcomplexes have been solved, no complete structure exists. Although NuRD complexes were initially identified as transcriptional repressors, it is now appreciated that they can act as activators as well (Williams et al, 2004; Bornelov et al, 2018; reviewed in Alendar and Berns, 2021). Although many components of the complex are able to interact with DNA and/or histones, recruitment of NuRD to target genes is predominantly mediated by interaction with transcription factors (reviewed in Alendar and Berns, 2021; Asmamaw et al, 2024);
In addition to being part of the NuRD complex, subfamily II CHD proteins may also be part of other chromatin modifying complexes, such as the CHD4-ChADH complex (Kaaij et al, 2019), and have indeed been shown to have chromatin sliding activity in vitro in the absence of interacting protein partners (Zhong et al, 2020; reviewed in Boulasiki et al, 2023; Alendar and Berns, 2021).

Literature References

PubMed ID	Title	Journal	Year
27806305	A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development Nitarska, J, Smith, JG, Sherlock, WT, Hillege, MM, Nott, A, Barshop, WD, Vashisht, AA, Wohlschlegel, JA, Mitter, R, Riccio, A	Cell Rep	2016
34725129	Sentinels of chromatin: chromodomain helicase DNA-binding proteins in development and disease Alendar, A, Berns, A	Genes Dev	2021
15189737	The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development Williams, CJ, Naito, T, Arco, PG, Seavitt, JR, Cashman, SM, De Souza, B, Qi, X, Keables, P, Von Andrian, UH, Georgopoulos, K	Immunity	2004
38081975	Energy-driven genome regulation by ATP-dependent chromatin remodellers Eustermann, S, Patel, AB, Hopfner, KP, He, Y, Korber, P	Nat Rev Mol Cell Biol	2024
9885572	NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities Xue, Y, Wong, J, Moreno, GT, Young, MK, Côté, J, Wang, W	Mol. Cell	1998
10444591	Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation Zhang, Y, Ng, HH, Erdjument-Bromage, H, Tempst, P, Bird, A, Reinberg, D	Genes Dev.	1999
9804427	Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex Tong, JK, Hassig, CA, Schnitzler, GR, Kingston, RE, Schreiber, SL	Nature	1998
38971208	Histone deacetylase complexes: Structure, regulation and function Asmamaw, MD, He, A, Zhang, LR, Liu, HM, Gao, Y	Biochim Biophys Acta Rev Cancer	2024
25825869	The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex Kolla, V, Naraparaju, K, Zhuang, T, Higashi, M, Kolla, S, Blobel, GA, Brodeur, GM	Biochem J	2015
16428440	MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties le Guezennec, X, Vermeulen, M, Brinkman, AB, Hoeijmakers, WA, Cohen, A, Lasonder, E, Stunnenberg, HG	Mol. Cell. Biol.	2006
31491387	The ChAHP Complex Counteracts Chromatin Looping at CTCF Sites that Emerged from SINE Expansions in Mouse Kaaij, LJT, Mohn, F, van der Weide, RH, de Wit, E, Buhler, M	Cell	2019
37190088	The NuRD Complex in Neurodevelopment and Disease: A Case of Sliding Doors Boulasiki, P, Tan, XW, Spinelli, M, Riccio, A	Cells	2023
30008319	The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression Bornelöv, S, Reynolds, N, Xenophontos, M, Gharbi, S, Johnstone, E, Floyd, R, Ralser, M, Signolet, J, Loos, R, Dietmann, S, Bertone, P, Hendrich, B	Mol Cell	2018
32251276	CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation Zhong, Y, Paudel, BP, Ryan, DP, Low, JKK, Franck, C, Patel, K, Bedward, MJ, Torrado, M, Payne, RJ, van Oijen, AM, Mackay, JP	Nat Commun	2020