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, Mi-2/NuRD was the only known protein complex that couples chromatin remodeling ATPase and chromatin deacetylation enzymatic functions.[3]

The NuRD complex contains seven subunits: the histone deacetylase core proteins HDAC1 and HDAC2, the histone-binding proteins RbAp46 and RbAp48, the metastasis-associated proteins MTA1 (or MTA2 / MTA3), the methyl-CpG-binding domain protein MBD3 (or MBD2) and the chromodomain-helicase-DNA-binding protein CHD3 (aka Mi-2alpha) or CHD4 (aka Mi-2beta).

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.[4][5]

Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs. Depletion of Mbd3, on the other hand, improves reprogramming efficiency only in fibroblast,[6][7] that results in deterministic and synchronized iPS cell reprogramming (near 100% efficiency within seven days from mouse and human cells).[8]

References
  1. Xue Y, Wong J, Moreno GT, Young MK, Côté J, Wang W (December 1998). "NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities". Molecular Cell. 2 (6): 851–61. doi:10.1016/S1097-2765(00)80299-3. PMID 9885572.
  2. Zhang Y, Yinghua L (2010). "The Expanding Mi-2/NuRD Complexes: A Schematic Glance". Proteomics Insights. 3: 79–109. doi:10.4137/PRI.S6329.
  3. Denslow SA, Wade PA (August 2007). "The human Mi-2/NuRD complex and gene regulation". Oncogene. 26 (37): 5433–8. doi:10.1038/sj.onc.1210611. PMID 17694084.
  4. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D (August 1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes & Development. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
  5. Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D (October 1998). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell. 95 (2): 279–89. doi:10.1016/S0092-8674(00)81758-4. PMID 9790534.
  6. Luo M, Ling T, Xie W, Sun H, Zhou Y, Zhu Q, Shen M, Zong L, Lyu G, Zhao Y, Ye T, Gu J, Tao W, Lu Z, Grummt I (July 2013). "NuRD blocks reprogramming of mouse somatic cells into pluripotent stem cells". Stem Cells. 31 (7): 1278–86. doi:10.1002/stem.1374. PMID 23533168.
  7. Drozd AM, Walczak MP, Piaskowski S, Stoczynska-Fidelus E, Rieske P, Grzela DP (June 2015). "Generation of human iPSCs from cells of fibroblastic and epithelial origin by means of the oriP/EBNA-1 episomal reprogramming system". Stem Cell Research & Therapy. 6 (1): 122. doi:10.1186/s13287-015-0112-3. PMC 4515927. PMID 26088261.
  8. Rais Y, Zviran A, Geula S, Gafni O, Chomsky E, Viukov S, Mansour AA, Caspi I, Krupalnik V, Zerbib M, Maza I, Mor N, Baran D, Weinberger L, Jaitin DA, Lara-Astiaso D, Blecher-Gonen R, Shipony Z, Mukamel Z, Hagai T, Gilad S, Amann-Zalcenstein D, Tanay A, Amit I, Novershtern N, Hanna JH (October 2013). "Deterministic direct reprogramming of somatic cells to pluripotency". Nature. 502 (7469): 65–70. doi:10.1038/nature12587. PMID 24048479.
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