MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties.
Xavier Le Guezennec,Michiel Vermeulen,Arie B. Brinkman,Wieteke A. M. Hoeijmakers,Adrian Cohen,Edwin Lasonder,Hendrik G. Stunnenberg +6 more
TLDR
Ch Chromatin immunoprecipitation experiments revealed that PRMT5 and MBD2 are recruited to CpG islands in a methylation-dependent manner in vivo and that H4R3, a substrate of PRMT, is methylated at these loci.Abstract:
The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into a physiological response. To gain insight into the function of MBD2 and MBD3, we first applied protein tagging and mass spectrometry. We show that MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like complexes, called MBD2/NuRD and MBD3/NuRD. We identified DOC-1, a putative tumor suppressor, as a novel core subunit of MBD2/NuRD as well as MBD3/NuRD. PRMT5 and its cofactor MEP50 were identified as specific MBD2/NuRD interactors. PRMT5 stably and specifically associates with and methylates the RG-rich N terminus of MBD2. Chromatin immunoprecipitation experiments revealed that PRMT5 and MBD2 are recruited to CpG islands in a methylation-dependent manner in vivo and that H4R3, a substrate of PRMT, is methylated at these loci. Our data show that MBD2/NuRD and MBD3/NuRD are distinct protein complexes with different biochemical and functional properties.read more
Citations
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Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation
TL;DR: This work uses nucleosomes methylated on DNA and on histone H3 in an affinity assay and a proteomic analysis to identify "crosstalk" between these two distinct classes of modification, establishing SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications.
Journal ArticleDOI
Deterministic direct reprogramming of somatic cells to pluripotency
Yoach Rais,Asaf Zviran,Shay Geula,Ohad Gafni,Elad Chomsky,Sergey Viukov,Abed AlFatah Mansour,Inbal Caspi,Vladislav Krupalnik,Mirie Zerbib,Itay Maza,Nofar Mor,Dror Baran,Leehee Weinberger,Diego Jaitin,David Lara-Astiaso,Ronnie Blecher-Gonen,Zohar Shipony,Zohar Mukamel,Tzachi Hagai,Shlomit Gilad,Daniela Amann-Zalcenstein,Amos Tanay,Ido Amit,Noa Novershtern,Jacob H. Hanna +25 more
TL;DR: The findings uncover a dichotomous molecular function for the reprogramming factors, serving to reactivate endogenous pluripotency networks while simultaneously directly recruiting the Mbd3/NuRD repressor complex that potently restrains the reactivation of OSKM downstream target genes.
Journal ArticleDOI
The human Mi-2/NuRD complex and gene regulation
S A Denslow,Paul A. Wade +1 more
TL;DR: A working model is proposed that integrates the known biochemical properties of the enzyme with emerging models on how chromatin structure and modification relate to gene activity.
Journal ArticleDOI
Mbd3/NURD Complex Regulates Expression of 5-Hydroxymethylcytosine Marked Genes in Embryonic Stem Cells
Ozlem Yildirim,Ruowang Li,Jui-Hung Hung,Poshen B Chen,Xianjun Dong,Ly-Sha Ee,Zhiping Weng,Oliver J. Rando,Thomas G. Fazzio +8 more
TL;DR: The roles of several chromatin regulators whose loss affects the pluripotent state of ES cells are examined, and it is found that Mbd3 and Brg1 antagonistically regulate a common set of genes by regulating promoter nucleosome occupancy.
Journal ArticleDOI
DNA methylation and methyl-CpG binding proteins: developmental requirements and function
TL;DR: The advances in the understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development are reviewed.
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