Genomic Maps and Comparative Analysis of Histone Modifications in Human and Mouse

We mapped histone H3 lysine 4 di- and trimethylation and lysine 9/14 acetylation across the nonrepetitive portions of human chromosomes 21 and 22 and compared patterns of lysine 4 dimethylation for several orthologous human and mouse loci. Both chromosomes show punctate sites enriched for modified histones. Sites showing trimethylation correlate with transcription starts, while those showing mainly dimethylation occur elsewhere in the vicinity of active genes. Punctate methylation patterns are also evident at the cytokine and IL-4 receptor loci. The Hox clusters present a strikingly different picture, with broad lysine 4-methylated regions that overlay multiple active genes. We suggest these regions represent active chromatin domains required for the maintenance of Hox gene expression. Methylation patterns at orthologous loci are strongly conserved between human and mouse even though many methylated sites do not show sequence conservation notably higher than background. This suggests that the DNA elements that direct the methylation represent only a small fraction of the region or lie at some distance from the site.

[1]  Stuart L Schreiber,et al.  Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. , 2003, Molecular cell.

[2]  D. Duboule,et al.  Organizing Axes in Time and Space; 25 Years of Colinear Tinkering , 2003, Science.

[3]  D. Haussler,et al.  Aligning multiple genomic sequences with the threaded blockset aligner. , 2004, Genome research.

[4]  David Botstein,et al.  Diversity, topographic differentiation, and positional memory in human fibroblasts , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[6]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[7]  Philip R. Gafken,et al.  Histone H3.3 is enriched in covalent modifications associated with active chromatin. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Danny Reinberg,et al.  Elongation by RNA polymerase II: the short and long of it. , 2004, Genes & development.

[9]  E. Lewis,et al.  Characterization of the intergenic RNA profile at abdominal-A and Abdominal-B in the Drosophila bithorax complex , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Groudine,et al.  A Complex Chromatin Landscape Revealed by Patterns of Nuclease Sensitivity and Histone Modification within the Mouse β-Globin Locus , 2003, Molecular and Cellular Biology.

[11]  Philip Lijnzaad,et al.  The Ensembl genome database project , 2002, Nucleic Acids Res..

[12]  S. P. Fodor,et al.  Large-Scale Transcriptional Activity in Chromosomes 21 and 22 , 2002, Science.

[13]  S. Schreiber,et al.  Development and validation of a T7 based linear amplification for genomic DNA , 2003, BMC Genomics.

[14]  David Landsman,et al.  High-resolution genome-wide mapping of histone modifications , 2004, Nature Biotechnology.

[15]  A. Wolffe,et al.  Epigenetics: regulation through repression. , 1999, Science.

[16]  Charles Kooperberg,et al.  The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. , 2004, Genes & development.

[17]  R. Kingston,et al.  Mechanisms of transcriptional memory , 2001, Nature Reviews Molecular Cell Biology.

[18]  P. Fraser,et al.  Antisense intergenic transcription in V(D)J recombination , 2004, Nature Immunology.

[19]  S. Korsmeyer,et al.  Altered Hox expression and segmental identity in Mll-mutant mice , 1995, Nature.

[20]  C. Allis,et al.  Translating the Histone Code , 2001, Science.

[21]  C. Allis,et al.  Histone and chromatin cross-talk. , 2003, Current opinion in cell biology.

[22]  Toshiki Mori,et al.  ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. , 2002, Molecular cell.

[23]  S. Cawley,et al.  Unbiased Mapping of Transcription Factor Binding Sites along Human Chromosomes 21 and 22 Points to Widespread Regulation of Noncoding RNAs , 2004, Cell.

[24]  Michael Hampsey,et al.  Tails of Intrigue Phosphorylation of RNA Polymerase II Mediates Histone Methylation , 2003, Cell.

[25]  M. Johnston,et al.  The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. , 2003, Molecular cell.

[26]  Thomas A Milne,et al.  MLL targets SET domain methyltransferase activity to Hox gene promoters. , 2002, Molecular cell.

[27]  Peter A. Jones,et al.  Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Tony Kouzarides,et al.  Histone H3 lysine 4 methylation patterns in higher eukaryotic genes , 2004, Nature Cell Biology.

[29]  S. Cawley,et al.  Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22. , 2004, Genome research.

[30]  C. Allis,et al.  Correlation Between Histone Lysine Methylation and Developmental Changes at the Chicken β-Globin Locus , 2001, Science.

[31]  S. Schreiber,et al.  Global nucleosome occupancy in yeast , 2004, Genome Biology.

[32]  R. Paro,et al.  Transcription through Intergenic Chromosomal Memory Elements of the Drosophila Bithorax Complex Correlates with an Epigenetic Switch , 2002, Molecular and Cellular Biology.

[33]  Stuart L. Schreiber,et al.  Methylation of histone H3 Lys 4 in coding regions of active genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[34]  S. Tillib,et al.  Modulation of heat shock gene expression by the TAC1 chromatin-modifying complex , 2004, Nature Cell Biology.

[35]  S. Schreiber,et al.  Signaling Network Model of Chromatin , 2002, Cell.

[36]  Nick Gilbert,et al.  Chromatin Architecture of the Human Genome Gene-Rich Domains Are Enriched in Open Chromatin Fibers , 2004, Cell.

[37]  Douglas A. Wolfe,et al.  Nonparametric Statistical Methods , 1973 .

[38]  Tom H. Pringle,et al.  The human genome browser at UCSC. , 2002, Genome research.

[39]  B. Turner,et al.  Cellular Memory and the Histone Code , 2002, Cell.

[40]  A. Feinberg,et al.  The history of cancer epigenetics , 2004, Nature Reviews Cancer.

[41]  Mouse Genome Sequencing Consortium.  Initial sequencing and comparative analysis of the mouse genome , 2002, Nature.

[42]  J. Lieb,et al.  Evidence for nucleosome depletion at active regulatory regions genome-wide , 2004, Nature Genetics.

[43]  P. Fraser,et al.  Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. , 2000, Molecular cell.

[44]  Kevin Struhl,et al.  Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. , 2003, Molecular cell.

[45]  Stuart L. Schreiber,et al.  Active genes are tri-methylated at K4 of histone H3 , 2002, Nature.

[46]  W. Bickmore,et al.  Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription. , 2004, Genes & development.

[47]  David L. Wheeler,et al.  GenBank: update , 2004, Nucleic Acids Res..