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Transcriptional features of genomic regulatory blocks

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Item Type:Article
Title:Transcriptional features of genomic regulatory blocks
Creators Name:Akalin, A. and Fredman, D. and Arner, E and Dong, X and Bryne, JC and Suzuki, H. and Daub, CO and Hayashizaki, Y and Lenhard, B
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.
Keywords:Acetylation, Base Sequence, Cell Differentiation, Conserved Sequence, CpG Islands, Gene Expression Regulation, Gene Regulatory Networks, Genetic Epigenesis, Genetic Models, Genetic Promoter Regions, Genetic Transcription, Human Genome, Macrophages, Nucleic Acid Regulatory Sequences, Transcription Initiation Site
Source:Genome Biology
ISSN:1474-760X
Publisher:BioMed Central (U.K.)
Volume:10
Number:4
Page Range:R38
Date:19 April 2009
Official Publication:https://doi.org/10.1186/gb-2009-10-4-r38
PubMed:View item in PubMed

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