title: Combinatorial effects of four histone modifications in transcription and differentiation.
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.
authors.affiliation: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Ihnestrasse 73, 14195 Berlin, Germany.
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Fischer
authors.forename: Joern
authors.initials: J
authors.lastname: Toedling
authors.forename: Tammo
authors.initials: T
authors.lastname: Krueger
authors.forename: Markus
authors.initials: M
authors.lastname: Schueler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.forename: Silke
authors.initials: S
authors.lastname: Sperling
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism*; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D006657:Histones; D009707:Nucleosomes