4.7 Article

Different distribution of histone modifications in genes with unidirectional and bidirectional transcription and a role of CTCF and cohesin in directing transcription

Journal

BMC GENOMICS
Volume 16, Issue -, Pages -

Publisher

BIOMED CENTRAL LTD
DOI: 10.1186/s12864-015-1485-5

Keywords

Antisense transcription; CTCF; RAD21; Cohesin; CAGE; Epigenetics; Transcription factor; Histone modification

Funding

  1. Swedish Research Council for Medicine and Health [A0350501]
  2. Swedish Research Council for Science and Technology [B0605201]
  3. Swedish Research Council FORMAS
  4. Polish Ministry of Science and Higher Education [N301 239536]
  5. Institute of Computer Science, PAN
  6. eSSENCE program

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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.

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