Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs
1 Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
2 MOE Key Lab of Bioinformatics and System Biology, Rm 2-111 Biotech Building, School of Life Sciences, Tsinghua University, Beijing, China 100084
3 Program in Computational Biology and Bioinformatics and Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
4 Department of Genetics, Stanford University School of Medicine, Mail Stop-5120, Stanford, CA 94305, USA
Genome Biology 2013, 14:R5 doi:10.1186/gb-2013-14-1-r5Published: 23 January 2013
The tumor suppressor Rb/E2F regulates gene expression to control differentiation in multiple tissues during development, although how it directs tissue-specific gene regulation in vivo is poorly understood.
We determined the genome-wide binding profiles for Caenorhabditis elegans Rb/E2F-like components in the germline, in the intestine and broadly throughout the soma, and uncovered highly tissue-specific binding patterns and target genes. Chromatin association by LIN-35, the C. elegans ortholog of Rb, is impaired in the germline but robust in the soma, a characteristic that might govern differential effects on gene expression in the two cell types. In the intestine, LIN-35 and the heterochromatin protein HPL-2, the ortholog of Hp1, coordinately bind at many sites lacking E2F. Finally, selected direct target genes contribute to the soma-to-germline transformation of lin-35 mutants, including mes-4, a soma-specific target that promotes H3K36 methylation, and csr-1, a germline-specific target that functions in a 22G small RNA pathway.
In sum, identification of tissue-specific binding profiles and effector target genes reveals important insights into the mechanisms by which Rb/E2F controls distinct cell fates in vivo.