Abstract
CAGE tag mapping of transcription start sites across different human tissues shows that genomic regulatory blocks have unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.
Highlights
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
This has led us to formulate the concept of genomic regulatory blocks (GRBs), which are functional regulatory units on a chromosome that are spanned by HCNEs and contain the gene regulated by HCNEs
Our results reveal that target and bystander gene expression is decoupled by means of their different responsiveness to long-range regulatory inputs, and that expression of target genes, unlike bystanders, is significantly associated with acetylation of anciently conserved HCNEs within the corresponding GRB
Summary
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. It has been demonstrated recently that the loci of many key developmental regulatory genes are spanned by arrays of highly conserved non-coding elements (HCNEs) [1,2] Many of these HCNEs function as long-range enhancers [3,4], collaboratively contributing to specific regulation of given target. We have shown that the regions of most anciently preserved synteny in vertebrates [6] and insects [7] are due to the requirement to keep such arrays of HCNEs in cis to their target genes This has led us to formulate the concept of genomic regulatory blocks (GRBs), which are functional regulatory units on a chromosome that are spanned by HCNEs and contain the gene regulated by HCNEs (the target gene). The functions and expression patterns of bystander genes are unrelated to those of the target gene, suggesting that they are unresponsive to the regulatory input of HCNEs [6,7,9]
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