bir-1, a Caenorhabditis elegans inhibitor-of-apoptosis gene homologous to Survivin is organized in an operon with the transcription cofactor C. elegans SKIP (skp-1). Because genes arranged in operons are frequently linked functionally, we have asked whether BIR-1 also functions in transcription. bir-1 inhibition resulted in multiple developmental defects that overlapped with C. elegans SKIP loss-of-function phenotypes: retention of eggs, dumpy, movement defects, and lethality. bir-1 RNA-mediated interference decreased expression of several gfp transgenes and the endogenous genes dpy-7 and hlh-1. Immunoblot analysis revealed decreased phosphoacetylated histones in bir-1 RNA-mediated interferencetreated worms. In a heterologous transfection system, BIR-1 augments thyroid hormone-regulated transcription and has an additive effect with SKIP. These results show that BIR-1 functions in the regulation of transcription and development. M odulation of specific gene transcription depends on orchestrated events involving the modification of chromatin and cooperation between RNA polymerase II and supporting factors. A large number of events participate in this process including the assembly of RNA polymerase II active complex on particular promoters, cooperation and modification of TFII transcription factors, and interactions with numerous cofactors (for review see ref. 1). Modification of chromatin proteins such as acetylation, methylation, and phosphorylation further influences transcription activation or repression and represents another level of regulation (2-6). Regulation of gene transcription includes complex chromatin reorganization. During this process, histones in promoter regions as well as proteins involved in transcription complex are modified covalently. Modification of histones H3 and H4 includes methylation, acetylation, and phosphorylation of N-terminal residues. A growing number of cofactors and specific enzymes with methyltransferase, acetyltransferase, and aminotransferase activity were shown recently also to precede acetylation and contribute to the activation of transcription (3,7,8). Phosphorylation of histones is part of mitotic chromosome condensation but was shown recently also to precede acetylation and contribute to the activation of transcription (9-13).The Caenorhabditis elegans baculoviral inhibitor-of-apoptosis repeat protein 1 (bir-1) gene in C. elegans encodes a homolog of the human gene Survivin (14,15). Survivin in mammals functions as an inhibitor of apoptosis (16). In C. elegans, bir-1 has only been linked thus far to spindle midzone formation and cytokinesis (14, 15). Our previous work noted that bir-1 is expressed from an operon with the transcription cofactor SKI-binding protein (SKIP; skp-1) (17). In C. elegans, genes expressed from an operon are often functionally linked (18,19), suggesting that bir-1 may also have a transcriptional function related to C. elegans SKIP (CeSKIP). CeSKIP is indispensable for C. elegans development, and its loss-of-function phenotype partially overlaps...