Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-3-2
pubmed:abstractText
Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish. We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers. Orthologous human and zebrafish enhancers underwent functional evolution within their sequence and often directed related but non-identical expression patterns. Despite an evolutionary distance of 450 million years, one pax6 HCNE drove expression in identical areas when comparing zebrafish vs. human HCNEs. HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1095-564X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
327
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
526-40
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes.
pubmed:affiliation
Sars Centre for Marine Molecular Biology, University of Bergen, 5008 Bergen, Norway.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't