Regulation of Fertility, Survival, and Cuticle Collagen Function by the Caenorhabditis elegans eaf-1 and ell-1 Genes

• Published in: The Journal of biological chemistry Vol. 286; no. 41; pp. 35915 - 35921
• Main Authors: Cai, Liquan, Phong, Binh L., Fisher, Alfred L., Wang, Zhou
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.10.2011; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Animals, Genetically Modified - genetics; Animals, Genetically Modified - metabolism; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - biosynthesis; Cell Line, Tumor; Collagen; Collagen - biosynthesis; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Gene Expression Regulation; Gene Regulation; Humans; Molecular Bases of Disease; Mutation; RNA Interference; Transcription Elongation Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcriptional Elongation Factors - genetics; Transcriptional Elongation Factors - metabolism; Tumor Suppressor Gene; Gene Regulation; Caenorhabditis elegans; Tumor Suppressor Gene; Collagen; Transcription Elongation Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111.270454

EAF2, an androgen-regulated protein, interacts with members of the ELL (eleven-nineteen lysine-rich leukemia) transcription factor family and also acts as a tumor suppressor. Although these proteins control transcriptional elongation and perhaps modulate the effects of other transcription factors, the mechanisms of their actions remain largely unknown. To gain new insights into the biology of the EAF2 and ELL family proteins, we used Caenorhabditis elegans as a model to explore the in vivo roles of their worm orthologs. Through the use of transgenic worms, RNAi, and an eaf-1 mutant, we found that both genes are expressed in multiple cell types throughout the worm life cycle and that they play important roles in fertility, survival, and body size regulation. ELL-1 and EAF-1 likely contribute to these activities in part through modulating cuticle synthesis, given that we observed a disrupted cuticle structure in ell-1 RNAi-treated or eaf-1 mutant worms. Consistent with disruption of cuticle structure, loss of either ELL-1 or EAF-1 suppressed the rol phenotype of specific collagen mutants, possibly through the control of dpy-3, dpy-13, and sqt-3 collagen gene expression. Furthermore, we also noted the regulation of collagen expression by ELL overexpression in PC3 human prostate cancer cells. Together, these results reveal important roles for the eaf-1 and ell-1 genes in the regulation of extracellular matrix components.