Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead.
The LSF/Grainyhead transcription factor family is involved in many important biological processes, including cell cycle, cell growth and development. In order to investigate the evolutionary conservation of these biological roles, we have characterized two new family members in Caenorhabditis elegans and Xenopus laevis. The C.elegans member, Ce-GRH-1, groups with the Grainyhead subfamily, while the X.laevis member, Xl-LSF, groups with the LSF subfamily. Ce-GRH-1 binds DNA in a sequence-specific manner identical to that of Drosophila melanogaster Grainyhead. In addition, Ce-GRH-1 binds to sequences upstream of the C.elegans gene encoding aromatic L-amino-acid decarboxylase and genes involved in post-embryonic development, mab-5 and dbl-1. All three C.elegans genes are homologs of D.melanogaster Grainyhead-regulated genes. RNA-mediated interference of Ce-grh-1 results in embryonic lethality in worms, accompanied by soft, defective cuticles. These phenotypes are strikingly similar to those observed previously in D.melanogaster grainyhead mutants, suggesting conservation of the developmental role of these family members over the course of evolution. Our phylogenetic analysis of the expanded LSF/GRH family (including other previously unrecognized proteins/ESTs) suggests that the structural and functional dichotomy of this family dates back more than 700 million years, i.e. to the time when the first multicellular organisms are thought to have arisen.
Venkatesan
Kavitha
K
Bioinformatics Program, Boston University, Boston, MA 02215, USA.
McManus
Heather R
HR
Mello
Craig C
CC
Smith
Temple F
TF
Hansen
Ulla
U
D024506:5' Flanking Region; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000196:embryology; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D020440:Gene Duplication; D005804:Genes, Lethal; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D010802:Phylogeny; D034622:RNA Interference; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029867:Xenopus Proteins
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C470734:EFF-1 protein, C elegans; C476427:GRH-1 protein, C elegans; C476428:LSF protein, Xenopus; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D029867:Xenopus Proteins; C062330:grh protein, Drosophila