Genomewide patterns of histone modifications in f

Authors: Indranil Sinha Marianna Wirén Karl Ekwall

Publish Date: 2006/03/03

Volume: 14, Issue: 1, Pages: 95-105

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Abstract

We have used oligonucleotide tiling arrays to construct genomewide highresolution histone acetylation maps for fission yeast The maps are corrected for nucleosome density and reveal surprisingly uniform patterns of modifications for five different histone acetylation sites We found that histone acetylation and methylation patterns are generally polar ie they change as a function of distance from the ATG codon A typical fission yeast gene shows a distinct peak of histone acetylation around the ATG and gradually decreased acetylation levels in the coding region The patterns are independent of gene length but dependent on the gene expression levels H3K9Ac shows a stronger peak near the ATG and is more reduced in the coding regions of genes with high expression compared with genes with low expression levels H4K16Ac is strongly reduced in coding regions of highly expressed genes A second microarray platform was used to confirm the 5′ to 3′ polarity effects observed with tiling microarrays By comparing coding region histone acetylation data in HDAC mutants and wild type we found that hos2 affects primarily the 5′ regions sir2 and clr6 affect middle regions and clr6 affects 3′ regions Thus mechanisms involving different HDACs modulate histone acetylation levels to maintain a 5′ to 3′ polarity within the coding regionsKE is a Royal Swedish Academy of Sciences Research Fellow supported by grants from Knut and Alice Wallenberg Foundation Swedish Cancer Society Swedish Research Council VR and the EU ‘Epigenome’ network of excellence We thank Michael Grunstein UCLA for kindly providing antibodies against acetylated histones and David Allis Rockefeller for kindly providing the H3K9Me2 antibody We thank Carolina Bonilla University College Sodertorn and Marika Rönnholm KI Dept Biosciences Novum for their kind help with microarray experiments We also thank all group members in particular Rebecca Silverstein for critical reading of the manuscript

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