title: Regulation of fertility, survival, and cuticle collagen function by the Caenorhabditis elegans eaf-1 and ell-1 genes.
abstract: 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.
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232.
authors: Liquan
authors: L
authors: Cai
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232.
authors: Binh L
authors: BL
authors: Phong
authors: Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15260. Electronic address: afisher@pitt.edu.
authors: Alfred L
authors: AL
authors: Fisher
authors: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania 15232. Electronic address: wangz2@upmc.edu.
authors: Zhou
authors: Z
authors: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D003094:Collagen / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C472771:EAF2 protein, human; C090862:ELL protein, human; C511741:SQT-3 protein, C elegans; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D003094:Collagen