TY - JOUR
T1 - MBD2/NuRD and MBD3/NuRD, two distinct complexes with different biochemical and functional properties
AU - Le Guezennec, Xavier
AU - Vermeulen, Michiel
AU - Brinkman, Arie B.
AU - Hoeijmakers, Wieteke A.M.
AU - Cohen, Adrian
AU - Lasonder, Edwin
AU - Stunnenberg, Hendrik G.
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=31344465966&partnerID=8YFLogxK
U2 - 10.1128/MCB.26.3.843-851.2006
DO - 10.1128/MCB.26.3.843-851.2006
M3 - Article
C2 - 16428440
AN - SCOPUS:31344465966
SN - 0270-7306
VL - 26
SP - 843
EP - 851
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 3
ER -