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Combinatorial patterns of histone acetylations and methylations in the human genome


Histones are characterized by numerous posttranslational modifications that influence gene transcription1,2. However, because of the lack of global distribution data in higher eukaryotic systems3, the extent to which gene-specific combinatorial patterns of histone modifications exist remains to be determined. Here, we report the patterns derived from the analysis of 39 histone modifications in human CD4+ T cells. Our data indicate that a large number of patterns are associated with promoters and enhancers. In particular, we identify a common modification module consisting of 17 modifications detected at 3,286 promoters. These modifications tend to colocalize in the genome and correlate with each other at an individual nucleosome level. Genes associated with this module tend to have higher expression, and addition of more modifications to this module is associated with further increased expression. Our data suggest that these histone modifications may act cooperatively to prepare chromatin for transcriptional activation.

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Figure 1: Three distribution patterns of histone acetylations.
Figure 2: Patterns of histone modifications associated with promoters.
Figure 3: Patterns of histone modifications at enhancers.
Figure 4: Correlation of histone modifications in the genome.
Figure 5: Characteristic spatial distribution of mutually exclusive modifications.

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We thank W. Leonard for comments. This work was supported by the Intramural Research Program of the US National Institutes of Health, National Heart, Lung, and Blood Institute (K.Z.) and by an NIH grant HG001696 (M.Q.Z.). J.A.R. is supported by an NIH training grant to New York University and a New York University McCracken Fellowship.

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Authors and Affiliations



Z.W. and K.Z. designed the study; Z.W. performed the experiments; A.B., S.C., K.C. and T.-Y.R. contributed to the study; C.Z., J.A.R, D.E.S., W.P. and M.Q.Z. analyzed the data; Z.W., J.A.R., W.P., M.Q.Z. and K.Z. wrote the paper.

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Correspondence to Keji Zhao.

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Wang, Z., Zang, C., Rosenfeld, J. et al. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40, 897–903 (2008).

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