MeCP2 in Rett syndrome: transcriptional repressor or chromatin architectural protein?

被引:34
作者
Chadwick, Lisa Helbling [1 ]
Wade, Paul A. [1 ]
机构
[1] Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA
关键词
D O I
10.1016/j.gde.2007.02.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Rett syndrome is a progressive neurological disorder caused by mutations in the methyl-DNA binding protein MeCP2. The longstanding model depicting MeCP2 as a transcriptional repressor predicts that the Rett syndrome phenotype probably results from misregulation of MeCP2 target genes. Somewhat unexpectedly, the identification of such targets has proven challenging. The recent identification of two MeCP2 targets, BDNF and DLX5, are suggestive of two very different roles for this protein - one as a classical repressor protein, and the other as a mediator of a complex, specialized chromatin structure.
引用
收藏
页码:121 / 125
页数:5
相关论文
共 38 条
  • [11] The Methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation
    Fuks, F
    Hurd, PJ
    Wolf, D
    Nan, XS
    Bird, AP
    Kouzarides, T
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (06) : 4035 - 4040
  • [12] Chromatin compaction by human MeCP2 - Assembly of novel secondary chromatin structures in the absence of DNA methylation
    Georgel, PT
    Horowitz-Scherer, RA
    Adkins, N
    Woodcock, CL
    Wade, PA
    Hansen, JC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) : 32181 - 32188
  • [13] Loss of silent-chromatin looping and impaired imprinting of DLX5 in Rett syndrome
    Horike, S
    Cai, ST
    Miyano, M
    Cheng, JF
    Kohwi-Shigematsu, T
    [J]. NATURE GENETICS, 2005, 37 (01) : 31 - 40
  • [14] Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
    Jones, PL
    Veenstra, GJC
    Wade, PA
    Vermaak, D
    Kass, SU
    Landsberger, N
    Strouboulis, J
    Wolffe, AP
    [J]. NATURE GENETICS, 1998, 19 (02) : 187 - 191
  • [15] Ube3a expression is not altered in Mecp2 mutant mice
    Jordan, ChaRandle
    Francke, Uta
    [J]. HUMAN MOLECULAR GENETICS, 2006, 15 (14) : 2210 - 2215
  • [16] The ski protein family is required for MeCP2-mediated transcriptional repression
    Kokura, K
    Kaul, SC
    Wadhwa, R
    Nomura, T
    Khan, MM
    Shinagawa, T
    Yasukawa, T
    Colmenares, C
    Ishii, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (36) : 34115 - 34121
  • [17] Gene expression analysis exposes mitochondrial abnormalities in a mouse model of Rett syndrome
    Kriaucionis, Skirmantas
    Paterson, Andrew
    CurtiS, John
    Guy, Jacky
    MacLeod, Nikki
    Bird, Adrian
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (13) : 5033 - 5042
  • [18] PURIFICATION, SEQUENCE, AND CELLULAR-LOCALIZATION OF A NOVEL CHROMOSOMAL PROTEIN THAT BINDS TO METHYLATED DNA
    LEWIS, JD
    MEEHAN, RR
    HENZEL, WJ
    MAURERFOGY, I
    JEPPESEN, P
    KLEIN, F
    BIRD, A
    [J]. CELL, 1992, 69 (06) : 905 - 914
  • [19] Epigenetic modifications in an imprinting cluster are controlled by a hierarchy of DMRs suggesting long-range chromatin interactions
    Lopes, S
    Lewis, A
    Hajkova, R
    Dean, W
    Oswald, J
    Forné, T
    Murrell, A
    Constancia, M
    Bartolomei, M
    Walter, J
    Reik, W
    [J]. HUMAN MOLECULAR GENETICS, 2003, 12 (03) : 295 - 305
  • [20] MeCP2 deficiency in Rett syndrome causes epigenetic aberrations at the PWS/AS imprinting center that affects UBE3A expression
    Makedonski, K
    Abuhatzira, L
    Kaufman, Y
    Razin, A
    Shemer, R
    [J]. HUMAN MOLECULAR GENETICS, 2005, 14 (08) : 1049 - 1058