Lsh, a member of the SNF2 family, is required for genome-wide methylation.

Methylation patterns of the mammalian genome are thought to be crucial for development. The precise mechanisms designating specific genomic loci for methylation are not known. Targeted deletion of Lsh results in perinatal lethality with a rather normal development. We report here, however, that Lsh(-/-) mice show substantial loss of methylation throughout the genome. The hypomethylated loci comprise repetitive elements and single copy genes. This suggests that global genomic methylation is not absolutely required for normal embryogenesis. Based on the similarity of Lsh to other SNF2 chromatin remodeling proteins, it suggests that alteration of chromatin affects global methylation patterns in mice.

[1]  J. P. Jackson,et al.  Requirement of CHROMOMETHYLASE3 for Maintenance of CpXpG Methylation , 2001, Science.

[2]  K. Muegge,et al.  Lsh, a SNF2 family member, is required for normal murine development. , 2001, Biochimica et biophysica acta.

[3]  R. Meehan,et al.  Loss of the maintenance methyltransferase, xDnmt1, induces apoptosis in Xenopus embryos , 2001, The EMBO journal.

[4]  R. Jaenisch,et al.  DNA Hypomethylation Perturbs the Function and Survival of CNS Neurons in Postnatal Animals , 2001, The Journal of Neuroscience.

[5]  S. Baylin,et al.  DNA methyltransferase levels and altered CpG methylation in the total genome and in the GSTP1 gene in human glioma cells transfected with sense and antisense DNA methyltransferase cDNA , 2000, Journal of cellular biochemistry.

[6]  G. Felsenfeld,et al.  Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene , 2000, Nature.

[7]  K. Muegge,et al.  Lsh, an SNF2/helicase family member, is required for proliferation of mature T lymphocytes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[8]  J. Workman,et al.  Promoter targeting and chromatin remodeling by the SWI/SNF complex. , 2000, Current opinion in genetics & development.

[9]  J. Herman,et al.  DNA hypermethylation in tumorigenesis: epigenetics joins genetics. , 2000, Trends in genetics : TIG.

[10]  D. Higgs,et al.  Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation , 2000, Nature Genetics.

[11]  K D Robertson,et al.  DNA methylation: past, present and future directions. , 2000, Carcinogenesis.

[12]  R. Meehan,et al.  Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. , 2000, Genes & development.

[13]  Issa Jp CpG-island methylation in aging and cancer. , 2000 .

[14]  J. Issa,et al.  CpG-island methylation in aging and cancer. , 2000, Current topics in microbiology and immunology.

[15]  N. Tommerup,et al.  Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene , 1999, Nature.

[16]  D. Haber,et al.  DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development , 1999, Cell.

[17]  E. Ballestar,et al.  Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation , 1999, Nature Genetics.

[18]  Paul Tempst,et al.  MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex , 1999, Nature Genetics.

[19]  G. Längst,et al.  Nucleosome Movement by CHRAC and ISWI without Disruption or trans-Displacement of the Histone Octamer , 1999, Cell.

[20]  Ali Hamiche,et al.  ATP-Dependent Histone Octamer Sliding Mediated by the Chromatin Remodeling Complex NURF , 1999, Cell.

[21]  S Ramchandani,et al.  DNA methylation is a reversible biological signal. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Jeddeloh,et al.  Maintenance of genomic methylation requires a SWI2/SNF2-like protein , 1999, Nature Genetics.

[23]  C. Walsh,et al.  Cytosine methylation and mammalian development. , 1999, Genes & development.

[24]  K. Muegge,et al.  Characterization of gene expression, genomic structure, and chromosomal localization of Hells (Lsh). , 1998, Genomics.

[25]  Colin A. Johnson,et al.  Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex , 1998, Nature.

[26]  M. Surani,et al.  Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells , 1997, The EMBO journal.

[27]  P. Jones,et al.  Altered DNA methylation and genome instability: a new pathway to cancer? , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Jaenisch,et al.  De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. , 1996, Development.

[29]  A. Razin,et al.  DNA Demethylation In Vitro: Involvement of RNA , 1996, Cell.

[30]  K. Muegge,et al.  A novel putative helicase produced in early murine lymphocytes. , 1996, Gene.

[31]  A. Razin,et al.  Gene methylation patterns and expression. , 1993, EXS.

[32]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[33]  A. Razin,et al.  Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. , 1992, Genes & development.

[34]  V. Chapman,et al.  Use of a HpaII-polymerase chain reaction assay to study DNA methylation in the Pgk-1 CpG island of mouse embryos at the time of X-chromosome inactivation , 1990, Molecular and cellular biology.

[35]  A. Razin,et al.  Direct detection of methylated cytosine in DNA by use of the restriction enzyme MspI. , 1979, Nucleic acids research.