Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing.
Transcriptional repression of methylated genes can be mediated by the methyl-CpG binding protein MeCP2. Here we show that human Brahma (Brm), a catalytic component of the SWI/SNF-related chromatin-remodeling complex, associates with MeCP2 in vivo and is functionally linked with repression. We used a number of different molecular approaches and chromatin immunoprecipitation strategies to show a unique cooperation between Brm, BAF57 and MeCP2. We show that Brm and MeCP2 assembly on chromatin occurs on methylated genes in cancer and the gene FMR1 in fragile X syndrome. These experimental findings identify a new role for SWI/SNF in gene repression by MeCP2.
Harikrishnan
K N
KN
The Alfred Medical Research and Education Precinct, Baker Medical Research Institute, Epigenetics in Human Health and Disease Laboratory, Second Floor, Commercial Road, Prahran, Victoria 3181, Australia.
Chow
Maggie Z
MZ
Baker
Emma K
EK
Pal
Sharmistha
S
Bassal
Sahar
S
Brasacchio
Daniella
D
Wang
Li
L
Craig
Jeff M
JM
Jones
Peter L
PL
Sif
Saïd
S
El-Osta
Assam
A
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D020868:Gene Silencing / Q000502:physiology*; D006657:Histones / Q000502:physiology; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C497683:FMR1 protein, human; C497684:Fmr1 protein, mouse; C497392:MECP2 protein, human; C497393:Mecp2 protein, mouse; C445179:SWI-SNF-B chromatin-remodeling complex; C086469:brm protein, Drosophila