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Cancer biology and NuRD: a multifaceted chromatin remodelling complex

Nature Reviews Cancer volume 11, pages 588–596 (2011)Cite this article

Subjects

Key Points

  • The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2) complex is a multisubunit chromatin remodelling complex that contains two core subunits (chromodomain-helicase-DNA-binding protein 3 (CHD3; also known as Mi-2α) and CHD4 (also known as Mi-2β), and histone deacetylase 1 (HDAC1) and HDAC2) with enzymatic functions. CHD3 and CHD4 catalyse ATP-dependent chromatin remodelling, and HDAC1 and HDAC2 mediate histone and protein deacetylation.

  • All subunits of the complex are encoded by multiple gene paralogues. Combinatorial assembly of these paralogues contributes to the targeting and function of the complex.

  • The metastasis-associated gene 1 (MTA1) subunit is widely overexpressed in many types of cancer and is associated with poor prognosis.

  • Unlike other chromatin remodelling complexes with well-defined roles in cancer, the NuRD complex can promote or suppress tumorigenesis depending on context.

  • NuRD complex recruitment to specific loci is mediated by multiple mechanisms, including recruitment by transcription factors and direct interaction with methylated DNA.

  • Emerging evidence suggests non-transcriptional roles of the NuRD complex in the maintenance of genome stability, including DNA replication, chromatin assembly and DNA repair.

Abstract

The nucleosome remodelling and histone deacetylase (NuRD; also known as Mi-2) complex regulates gene expression at the level of chromatin. The NuRD complex has been identified — using both genetic and molecular analyses — as a key determinant of differentiation in mouse embryonic stem cells and during development in various model systems. Similar to other chromatin remodellers, such as SWI/SNF and Polycomb complexes, NuRD has also been implicated in the regulation of transcriptional events that are integral to oncogenesis and cancer progression. Emerging molecular details regarding the recruitment of NuRD to specific loci during development, and the modulation of these events in cancer, are used to illustrate how the inappropriate localization of the complex could contribute to tumour biology.

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Figure 1: Mechanisms by which the NuRD complex interacts with different factors to promote cancer development.
Figure 2: Non-transcriptional mechanisms by which the NuRD complex maintains genome stability.

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Acknowledgements

The authors would like to thank members of the Wade laboratory for critical comments and suggestions for this manuscript. They apologize to those whose work is not cited owing to space limitations. The authors' research is funded by the Intramural Research Program of the US National Institute of Environmental Health Sciences, NIH (Project number Z01ES101965 to P.A.W.).

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Lai, A., Wade, P. Cancer biology and NuRD: a multifaceted chromatin remodelling complex. Nat Rev Cancer 11, 588–596 (2011). https://doi.org/10.1038/nrc3091

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