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  Combinatorial effects of four histone modifications in transcription and differentiation

Fischer, J. J., Toedling, J., Krueger, T., Schueler, M., Huber, W., & Sperling, S. (2008). Combinatorial effects of four histone modifications in transcription and differentiation. Genomics, 91(1), 41-51. doi:10.1016/j.ygeno.2007.08.010.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-80B7-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-80B8-D
Genre: Journal Article

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 Creators:
Fischer, Jenny J.1, Author              
Toedling, Joern, Author
Krueger, Tammo2, Author
Schueler, Markus1, Author              
Huber, Wolfgang, Author
Sperling, Silke1, Author              
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
2Max Planck Society, ou_persistent13              

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Free keywords: ChIP, chromatin immunoprecipitation; ChIP–chip, chromatin immunoprecipitation followed by microarray analysis; GO, Gene Ontology;H3ac, histone 3 acetylated at lysine residues 9 and 14; H3K4me2, histone 3 dimethylated at lysine 4; H3K4me3, histone 3 trimethylated at lysine 4; H4ac, histone 4 acetylated at lysine residues 5, 8, 12, and 16; TSS, transcription start site
 Abstract: Nucleosomes are involved in DNA compaction and transcriptional regulation. Yet it is unclear whether histone modification marks are primary or secondary to transcription and whether they interact to form a histone code. We investigated the relationship between transcription and four histone modifications (H4ac, H3ac, H3K4me2/3) using ChIP–chip and expression microarray readouts from two murine cell lines, one in two differentiation stages. We found that their association with transcript levels strongly depends on the combination of histone modifications. H3K4me2 coincides with elevated expression levels only in combination with acetylation, while H3ac positive association is diminished by co-occurring modifications. During differentiation, upregulated transcripts frequently gain H4ac, while most modification conversions are uncorrelated with expression changes. Our results suggest histone modifications form a code, as their combinatorial composition is associated with distinct readouts. Histones may primarily function as signaling marks for specific effectors rather than being a sufficient driving force for or a consequence of transcription.

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Language(s): eng - English
 Dates: 2008-01
 Publication Status: Published in print
 Pages: -
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Title: Genomics
Source Genre: Journal
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Pages: - Volume / Issue: 91 (1) Sequence Number: - Start / End Page: 41 - 51 Identifier: ISSN: 0888-7543