In the field of

molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

, the Mi-2/NuRD (Nucleosome Remodeling Deacetylase) complex, is a group of associated proteins with both ATP-dependent

chromatin remodeling Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out ...

and

histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important becaus ...

activities. , Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.

Discovery

In 1998, several independent groups reported the discovery of multi-enzyme complexes conferring both nucleosome remodelling and histone deacetylation activities. Xue et al first described the human complex as the Nucleosome Remodelling and Deacetylase (NuRD) - this name has since been adopted for homologous complexes in most organisms.

Composition

The NuRD

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

contains seven subunits: the histone deacetylase core proteins

HDAC1 Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the ''HDAC1'' gene. Function Histone acetylation and deacetylation, catalyzed by multisubunit complexes, play a key role in the regulation of eukaryotic gene expression. ...

and

HDAC2 Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the ''HDAC2'' gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the ...

, the histone-binding proteins RbAp46 and

RbAp48 Histone-binding protein RBBP4 (also known as RbAp48, or NURF55) is a protein that in humans is encoded by the ''RBBP4'' gene. Function This gene encodes a ubiquitously expressed nuclear protein that belongs to a highly conserved subfamily of ...

, the metastasis-associated proteins

MTA1 Metastasis-associated protein MTA1 is a protein that in humans is encoded by the ''MTA1'' gene. MTA1 is the founding member of the MTA family of genes. MTA1 is primarily localized in the nucleus but also found to be distributed in the extra-nuc ...

(or

MTA2 Metastasis-associated protein MTA2 is a protein that in humans is encoded by the ''MTA2'' gene. MTA2 is the second member of the MTA family of genes. MTA2 protein localizes in the nucleus and is a component of the nucleosome remodeling and the ...

MTA3 Metastasis-associated protein MTA3 is a protein that in humans is encoded by the ''MTA3'' gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate ( NuR ...

), the methyl-CpG-binding domain protein

MBD3 Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the ''MBD3'' gene. Function DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins ME ...

(or

MBD2 Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the ''MBD2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in D ...

) and the chromodomain-helicase-DNA-binding protein

CHD3 Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the ''CHD3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleot ...

(aka Mi-2alpha) or

CHD4 Chromodomain-helicase-DNA-binding protein 4 is an enzyme that in humans is encoded by the ''CHD4'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleo ...

(aka Mi-2beta). NuRD can be subdivided into two discrete subcomplexes which confer neuclosome remodelling or histone deacetylation activity,each of which retains catalytic activity without the presence of the other. The histone deacetylases

and

and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes.

NuRD-independent Mi2/CHD4 activity

Mi-2/CHD4 may confer NuRD independent transcriptional regulation in some organisms and contexts. For example, in the fly, ''Drosophila melanogaster'', the majority of Mi2 biochemically purifies separately from the rest of the NuRD subunits and profiling of NuRD component binding sites indicates that only a minority of loci are co-occupied by both Mi-2 and HDAC. Similar results are reported in mouse embryonic stem cells where CHD4 shares only a minority of binding loci with core NuRD component, MBD3. Independently of histone deacetylase, Mi-2 knockdown in neuronal tissue results in mis-expression of genes that are normally restricted to germline. A similar observation was made in human erythroid cells, in which CHD4 but not Mi-2 is required for suppression of fetal globin genes.

Biological functions of NuRD

NuRD is traditionally thought of as a primarily repressive complex (in AP-1 Sagy, N., Meyrom, N., Beckerman, P. et al. Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression. Clin Epigenet 16, 27 (2024). https://doi.org/10.1186/s13148-024-01642-w), and in some contexts it is clear that it does confer this function. For example, NuRD is required to silence genes in neuronal differentiation. However, more recent studies have presented a more nuanced picture of NuRD activity in which it is required for fine-tuning of gene expression during stem cell differentiation to ensure appropriate lineage specification.

References

{{reflist, 33em Protein complexes