Mi-2/NuRD complex
In the field of molecular biology, the Mi-2/NuRD (Nucleosome Remodeling Deacetylase) complex, is a group of associated proteins with both ATP-dependent chromatin remodeling and histone deacetylase activities.[1][2] As of 2007[update], Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.[3]
Discovery
In 1998, several independent groups reported the discovery of multi-enzyme complexes conferring both nucleosome remodelling and histone deacetylation activities.[4][5][6][7] Xue et al[1] 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
(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.[8] The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes.[9][10]
NuRD-independent Mi2/CHD4 activity
Mi-2/CHD4 may confer NuRD independent transcriptional regulation in some organisms and contexts.[11] For example, in the fly, Drosophila melanogaster, the majority of Mi2 biochemically purifies separately from the rest of the NuRD subunits[12] and profiling of NuRD component binding sites indicates that only a minority of loci are co-occupied by both Mi-2 and HDAC.[13] Similar results are reported in mouse embryonic stem cells where CHD4 shares only a minority of binding loci with core NuRD component, MBD3.[14] Independently of histone deacetylase, Mi-2 knockdown in neuronal tissue results in mis-expression of genes that are normally restricted to germline.[13] A similar observation was made in human erythroid cells, in which CHD4 but not Mi-2 is required for suppression of fetal globin genes.[15]
Biological functions of NuRD
NuRD is traditionally thought of as a primarily repressive complex, and in some contexts it is clear that it does confer this function. For example, NuRD is required to silence genes in neuronal differentiation.[16] 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.[14]
Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency only in fibroblast,[17][18][dubious ] that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells).[19][dubious ]
