BIR-1, the homologue of human Survivin, regulates expression of developmentally active collagen genes in C. elegans.
BIR-1 and Survivin are highly conserved members of the inhibitor of apoptosis protein family that regulate cell division in nematodes and mammals and inhibit apoptosis in mammals. In the C. elegans genome, bir-1 is organized in an operon together with transcription and splicing cofactor CeSKIP (skp-1) and is highly expressed during embryogenesis as well as in non-dividing cells during larval development. Previously we have shown that BIR-1 regulates transcription and development and its loss-of-function phenotype overlaps with loss of function of CeSKIP and nuclear hormone receptor CHR3 (NHR-23). Here we searched for genes whose expression is affected by BIR-1 loss of function using whole-genome microarray experiments and identified several collagen genes as candidate targets of bir-1 inhibition in L1 larval stage. The decreased expression of selected collagen genes in bir-l-inhibited larvae was confirmed by quantitative RT-PCR. Next, we generated transgenic lines expressing bir-1 mRNA under a heat shock-regulated promoter and tested whether bir-1 overexpression has the potential to augment the expression of genes that showed decreased expression in worms treated with bir-1 RNAi. Overexpression of bir-1 resulted in a pronounced increase (2 to 5 times) of the expression of these genes. Our findings support the concept that BIR-1, a protein generally regarded as a mitotic factor, is involved in the regulation of transcription during normal development of C. elegans and has a strong ability to affect transcription of developmentally active genes if overexpressed.
Libý
P
P
Laboratory of Molecular Pathology, Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
Pohludka
M
M
Vohánka
J
J
Kostrouchová
M
M
Kostrouch
D
D
Kostrouchová
M
M
Rall
J E
JE
Kostrouch
Z
Z
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003094:Collagen / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007814:Larva / Q000378:metabolism; D046228:Microarray Analysis; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D034622:RNA Interference; D015203:Reproducibility of Results; D017385:Sequence Homology; D000077022:Survivin; D014158:Transcription, Genetic
C107489:BIRC5 protein, human; D029742:Caenorhabditis elegans Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C118999:bir-1 protein, C elegans; D003094:Collagen