Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes
| Autor: | Pavla Navratilova, David Fredman, Katherine J. Turner, Thomas Becker, Boris Lenhard, Thomas A. Hawkins |
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| Rok vydání: | 2009 |
| Předmět: |
IMMP1L
animal structures PAX6 Transcription Factor Tol2 transposon cis-regulation Computational biology CTCF insulator Mice Transcription (biology) biology.animal Animals Humans Paired Box Transcription Factors Regulatory Elements Transcriptional Transgenes Eye Proteins Enhancer Molecular Biology Zebrafish Synteny Homeodomain Proteins Genetics Binding Sites biology RCN1 SOXB1 Transcription Factors ELP4 Gene Expression Regulation Developmental Vertebrate Cell Biology Zebrafish Proteins biology.organism_classification WT1 Repressor Proteins CTCF PAX6 Transcription Factor Gene Transcription Developmental Biology |
| Zdroj: | Developmental Biology. 327:526-540 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2008.10.044 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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