Human developmental enhancers conserved between deuterostomes and protostomes

PLoS Genet. 2012;8(8):e1002852. doi: 10.1371/journal.pgen.1002852. Epub 2012 Aug 2.

Abstract

The identification of homologies, whether morphological, molecular, or genetic, is fundamental to our understanding of common biological principles. Homologies bridging the great divide between deuterostomes and protostomes have served as the basis for current models of animal evolution and development. It is now appreciated that these two clades share a common developmental toolkit consisting of conserved transcription factors and signaling pathways. These patterning genes sometimes show common expression patterns and genetic interactions, suggesting the existence of similar or even conserved regulatory apparatus. However, previous studies have found no regulatory sequence conserved between deuterostomes and protostomes. Here we describe the first such enhancers, which we call bilaterian conserved regulatory elements (Bicores). Bicores show conservation of sequence and gene synteny. Sequence conservation of Bicores reflects conserved patterns of transcription factor binding sites. We predict that Bicores act as response elements to signaling pathways, and we show that Bicores are developmental enhancers that drive expression of transcriptional repressors in the vertebrate central nervous system. Although the small number of identified Bicores suggests extensive rewiring of cis-regulation between the protostome and deuterostome clades, additional Bicores may be revealed as our understanding of cis-regulatory logic and sample of bilaterian genomes continue to grow.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Biological Evolution
  • Central Nervous System / embryology
  • Central Nervous System / metabolism
  • Conserved Sequence
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Developmental
  • Genome*
  • Humans
  • Invertebrates / embryology
  • Invertebrates / genetics*
  • Invertebrates / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • Sequence Alignment
  • Signal Transduction
  • Synteny
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Vertebrates / embryology
  • Vertebrates / genetics*
  • Vertebrates / metabolism

Substances

  • Transcription Factors