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.
Bernstein
Bradley E
BE
Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. bbernst@fas.harvard.edu
Kamal
Michael
M
Lindblad-Toh
Kerstin
K
Bekiranov
Stefan
S
Bailey
Dione K
DK
Huebert
Dana J
DJ
McMahon
Scott
S
Karlsson
Elinor K
EK
Kulbokas
Edward J
EJ
Gingeras
Thomas R
TR
Schreiber
Stuart L
SL
Lander
Eric S
ES
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping / Q000379:methods; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000378:metabolism; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics* / Q000378:metabolism; D016678:Genome; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D019948:Receptors, Interleukin-4 / Q000235:genetics
D002843:Chromatin; D006657:Histones; D018398:Homeodomain Proteins; D019948:Receptors, Interleukin-4; D008239:Lysine