Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate distinct somatic and germline programs.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Michelle
M
Kudron
Wei
W
Niu
Zhi
Z
Lu
Guilin
G
Wang
Mark
M
Gerstein
Michael
M
Snyder
Valerie
V
Reinke
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D009928:Organ Specificity; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D050684:E2F Transcription Factors; C514742:HPL-2 protein, C elegans; D006657:Histones; C449639:Mes-4 protein, C elegans; D012097:Repressor Proteins; C116485:lin-35 protein, C elegans