title: Different distribution of histone modifications in genes with unidirectional and bidirectional transcription and a role of CTCF and cohesin in directing transcription.
abstract: BACKGROUND
  Several post-translational histone modifications are mainly found in gene promoters and are associated with the promoter activity. It has been hypothesized that histone modifications regulate the transcription, as opposed to the traditional view with transcription factors as the key regulators. Promoters of most active genes do not only initiate transcription of the coding sequence, but also a substantial amount of transcription of the antisense strand upstream of the transcription start site (TSS). This promoter feature has generally not been considered in previous studies of histone modifications and transcription factor binding.
  
  
  RESULTS
  We annotated protein-coding genes as bi- or unidirectional depending on their mode of transcription and compared histone modifications and transcription factor occurrences between them. We found that H3K4me3, H3K9ac, and H3K27ac were significantly more enriched upstream of the TSS in bidirectional genes compared with the unidirectional ones. In contrast, the downstream histone modification signals were similar, suggesting that the upstream histone modifications might be a consequence of transcription rather than a cause. Notably, we found well-positioned CTCF and RAD21 peaks approximately 60-80 bp upstream of the TSS in the unidirectional genes. The peak heights were related to the amount of antisense transcription and we hypothesized that CTCF and cohesin act as a barrier against antisense transcription.
  
  
  CONCLUSIONS
  Our results provide insights into the distribution of histone modifications at promoters and suggest a novel role of CTCF and cohesin as regulators of transcriptional direction.
authors.affiliation: Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, SE-751 24, Sweden. susanne.bornelov@imbim.uu.se.|Current affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, SE-751 23, Sweden. susanne.bornelov@imbim.uu.se.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bornelöv
authors.affiliation: Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, SE-751 24, Sweden. jan.komorowski@icm.uu.se.|Institute of Computer Science, Polish Academy of Sciences, Warsaw, 01-248, Poland. jan.komorowski@icm.uu.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Komorowski
authors.affiliation: Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SE-751 08, Sweden. claes.wadelius@igp.uu.se.
authors.forename: Claes
authors.initials: C
authors.lastname: Wadelius
mesh_terms: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020014:K562 Cells; D009687:Nuclear Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D000097722:Cohesins
chemical_list: D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012097:Repressor Proteins; D000097722:Cohesins; C000619697:CTCF protein, human; C429022:RAD21 protein, human