Evolving role of MeCP2 in Rett syndrome and autism.
Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2. Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome, the understanding of MeCP2 function has evolved. Although MeCP2 was predicted to be a global transcriptional repressor of methylated promoters, large-scale combined epigenomic approaches of MeCP2 binding, methylation and gene expression have demonstrated that MeCP2 binds preferentially to intergenic and intronic regions, and sparsely methylated promoters of active genes. This review compares the evolution of thought within two ‘classic’ epigenetic mechanisms of parental imprinting and X chromosome inactivation to that of the MeCP2 field, and considers the future relevance of integrated epigenomic databases to understanding autism and Rett syndrome.
LaSalle
Janine M
JM
Medical Microbiology and Immunology and Rowe Program in Human Genetics, University of California Davis School of Medicine, Davis, CA 95616, USA. jmlasalle@ucdavis.edu
Yasui
Dag H
DH
D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D041321:Chromosomes, Human, X; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D011401:Promoter Regions, Genetic; D015518:Rett Syndrome / Q000378:metabolism* / Q000473:pathology
D018398:Homeodomain Proteins; D051783:Methyl-CpG-Binding Protein 2; C088144:HoxA protein
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19416-21
18042715
Pediatr Neurol. 2003 Mar;28(3):205-11
12770674
Hum Mol Genet. 2007 Mar 15;16(6):640-50
17309881
Hum Mol Genet. 2004 Mar 15;13(6):629-39
14734626
Nature. 2008 Sep 11;455(7210):237-41
18668038
Curr Opin Cell Biol. 2006 Jun;18(3):307-16
16687245
Nucleic Acids Res. 2000 May 15;28(10):2201-6
10773092
Neuroreport. 1994 Jul 21;5(12):1509-13
7948850
Science. 2008 May 30;320(5880):1224-9
18511691
Hum Mol Genet. 2005 Jan 15;14(2):205-20
15548546
Hum Mol Genet. 2005 Feb 15;14(4):483-92
15615769
Nat Genet. 2006 Nov;38(11):1348-54
17033623
Nature. 1993 Nov 25;366(6453):362-5
8247133
Science. 2009 May 15;324(5929):929-30
19372393
Nat Genet. 2005 Jan;37(1):31-40
15608638
Nature. 1998 May 28;393(6683):386-9
9620804
Hum Mol Genet. 2005 Apr 15;14(8):1049-58
15757975
BMC Med Genet. 2007 Jun 20;8:36
17584923
Nat Genet. 2005 Mar;37(3):254-64
15696166
Annu Rev Genet. 2008;42:733-72
18729722
Ment Retard Dev Disabil Res Rev. 2002;8(2):94-8
12112734
Hum Mol Genet. 2008 Jun 15;17(12):1718-27
18321864
BMC Med Genet. 2002 Nov 5;3:12
12418965
Nature. 2008 Oct 16;455(7215):919-23
18923514
Mol Cell Biol. 2000 May;20(9):3316-29
10757815
Curr Opin Cell Biol. 2007 Jun;19(3):281-9
17467259
Nat Genet. 1998 Jun;19(2):187-91
9620779
Cell. 1997 Feb 21;88(4):471-81
9038338
BMC Biol. 2004 Sep 20;2:21
15377381
Nat Genet. 2009 Feb;41(2):178-186
19151715
Genes Dev. 2006 Aug 15;20(16):2223-37
16912274
Nature. 2008 Oct 16;455(7215):912-8
18923513
J Child Neurol. 2005 Sep;20(9):747-53
16225830
Genome Res. 2006 Feb;16(2):157-63
16365381
J Biol Chem. 2004 Nov 5;279(45):46490-6
15322089
Nature. 2008 Aug 7;454(7205):766-70
18600261
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7688-93
16682630
Am J Hum Genet. 2007 Sep;81(3):492-506
17701895
Cell. 2008 May 2;133(3):523-36
18423832
J Autism Dev Disord. 2005 Feb;35(1):117-27
15796127
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):671-8
19139413
N Biotechnol. 2009 Apr;25(4):195-203
19429539
Epidemiology. 2009 Jan;20(1):84-90
19234401
Nat Rev Genet. 2006 Feb;7(2):85-97
16418744
Curr Opin Genet Dev. 2007 Oct;17(5):408-14
17913490
Am J Med Genet A. 2004 Nov 15;131(1):1-10
15389703
Genet Med. 2000 Mar-Apr;2(2):131-5
11397326
Mol Cell. 2005 Sep 2;19(5):667-78
16137622
J Med Genet. 2009 Apr;46(4):242-8
18805830
J Biol Chem. 2003 Feb 7;278(6):4035-40
12427740
Hum Genet. 2002 Jun;110(6):545-52
12107440
Hum Mol Genet. 2009 Feb 1;18(3):525-34
19000991
J Cell Mol Med. 2008 Aug;12(4):1188-91
18537997
Hum Mol Genet. 2005 Mar 15;14(6):785-97
15689352
PLoS One. 2008;3(11):e3669
18989361
Neurobiol Dis. 2010 May;38(2):181-91
18840528
Oncogene. 2003 Jul 17;22(29):4509-16
12881707
EMBO Rep. 2005 Feb;6(2):128-33
15689940
Hum Mol Genet. 2007 Mar 15;16(6):691-703
17339270
Science. 2004 Jul 23;305(5683):525-8
15273396
Neurology. 2002 Jan 22;58(2):226-30
11805248
J Neuropathol Exp Neurol. 2005 Nov;64(11):925-35
16254487
Science. 2003 Oct 31;302(5646):890-3
14593184
Hum Mol Genet. 2005 Aug 1;14(15):2247-56
16002417
J Med Genet. 2000 Dec;37(12):E41
11106359
Nat Genet. 1999 Oct;23(2):185-8
10508514
Hum Mol Genet. 2006 Jun 15;15(12):2003-14
16682435
Neuron. 2006 Oct 19;52(2):255-69
17046689
Science. 2007 Feb 23;315(5815):1141-3
17322062
Mamm Genome. 2008 Aug;19(7-8):493-502
18815833
Nat Rev Genet. 2007 Apr;8(4):253-62
17363974
Cell. 1984 May;37(1):179-83
6722870
Science. 2003 Oct 31;302(5646):885-9
14593183
Science. 2009 May 15;324(5929):930-5
19372391
Nucleic Acids Res. 2004 Aug 09;32(14):4100-8
15302911
Nature. 2008 Mar 13;452(7184):215-9
18278030
Science. 2007 Nov 16;318(5853):1136-40
18006746
Neuron. 2006 Feb 2;49(3):341-8
16446138
Am J Med Genet. 1999 Feb 12;82(4):294-300
10051161
J Neuropathol Exp Neurol. 1998 Nov;57(11):1013-7
9825937
Cell. 2008 Mar 7;132(5):721-3
18329356
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15536-41
12432090
Horm Res. 2009 Apr;71 Suppl 2:30-5
19407494
Nature. 2009 May 7;459(7243):108-12
19295514
Cancer Res. 2009 Feb 15;69(4):1527-35
19190346
Biochem Cell Biol. 2006 Aug;84(4):505-17
16936823
Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17551-8
16251272
Am J Hum Genet. 1997 Apr;60(4):928-34
9106540
Cell Mol Life Sci. 2004 Sep;61(17):2163-7
15338046
Epigenetics. 2006 Oct-Dec;1(4):e1-11
17486179
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2709-14
17296936
Acta Neuropathol. 1996;91(1):117-9
8773156
Nat Genet. 2004 Sep;36(9):949-51
15286789
Nat Genet. 2007 Apr;39(4):457-66
17334365
Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18267-72
17108082
Science. 2008 Jul 11;321(5886):218-23
18621663
Curr Top Dev Biol. 2004;59:61-86
14975247
J Neurosci. 2006 Jan 4;26(1):319-27
16399702
J Biol Chem. 2003 Aug 22;278(34):32181-8
12788925
Nature. 2008 Sep 11;455(7210):232-6
18668039
Nat Rev Genet. 2008 Jun;9(6):465-76
18463664
Cell. 2008 Oct 31;135(3):391-5
18984147
Cell. 1992 Jun 12;69(6):905-14
1606614
Hum Mol Genet. 1999 Jun;8(6):1025-37
10332034
Am J Hum Genet. 2005 Sep;77(3):442-53
16080119
Reprod Toxicol. 2007 Apr-May;23(3):297-307
17046196
Cell Mol Life Sci. 2007 Apr;64(7-8):947-60
17347796
Biol Psychiatry. 2009 Aug 15;66(4):349-59
19278672
Nat Methods. 2007 Nov;4(11):895-901
17971780
Nature. 2005 Mar 17;434(7031):400-4
15772666
J Med Genet. 2009 Feb;46(2):86-93
18835857
Eur J Hum Genet. 2004 Jan;12(1):24-8
14560307
Science. 2007 Apr 20;316(5823):445-9
17363630
Cytogenet Genome Res. 2006;113(1-4):144-52
16575174