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Open Access Highly Accessed Research

Transcriptional features of genomic regulatory blocks

Altuna Akalin1, David Fredman13, Erik Arner2, Xianjun Dong1, Jan Christian Bryne1, Harukazu Suzuki2, Carsten O Daub2, Yoshihide Hayashizaki2 and Boris Lenhard1*

Author Affiliations

1 Computational Biology Unit, Bergen Center for Computational Science, and Sars Centre for Marine Molecular Biology, University of Bergen, 5008 Bergen, Norway

2 RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

3 Current address: Department for Molecular Evolution and Development, Centre for Organismal Systems Biology, Faculty of Life Sciences, University of Vienna, Althanstrasse, 1090 Wien, Austria

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Genome Biology 2009, 10:R38  doi:10.1186/gb-2009-10-4-r38

Published: 19 April 2009

Abstract

Background

Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. The tight regulation of target genes, complex arrangement of regulatory inputs, and the differential responsiveness of genes in the region call for the examination of fundamental rules governing transcriptional activity in GRBs. Here we use extensive CAGE tag mapping of transcription start sites across different human tissues and differentiation stages combined with expression data and a number of sequence and epigenetic features to discover these rules and patterns.

Results

We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region. Additionally, target gene promoters have a distinct combination of activating and repressing histone modifications in mouse embryonic stem cell lines.

Conclusions

GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.