Nucleic Acids Research, 2003, Vol. 31, No. 15 4304-4316
© 2003 Oxford University Press
Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead
1 Bioinformatics Program, 2 Biomolecular Engineering Research Center and 3 Department of Biology, Boston University, Boston, MA 02215, USA and 4 Howard Hughes Medical Institute, University of Massachusetts, Worcester, MA 01605, USA
*To whom correspondence should be addressed at Department of Biology, 5 Cummington Street, Boston University, Boston, MA 02215, USA. Tel: +1 617 353 8730; Fax: +1 617 353 8734; Email: uhansen{at}bu.edu
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.
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