Transcription of bxd Noncoding RNAs Promoted by Trithorax Represses Ubx in cis by Transcriptional Interference

Abstract

Much of the genome is transcribed into long noncoding RNAs (ncRNAs). Previous data suggested that bithoraxoid (bxd) ncRNAs of the Drosophila bithorax complex (BX-C) prevent silencing of Ultrabithorax (Ubx) and recruit activating proteins of the trithorax group (trxG) to their maintenance elements (MEs). We found that, surprisingly, Ubx and several bxd ncRNAs are expressed in nonoverlapping patterns in both embryos and imaginal discs, suggesting that transcription of these ncRNAs is associated with repression, not activation, of Ubx. Our data rule out siRNA or miRNA-based mechanisms for repression by bxd ncRNAs. Rather, ncRNA transcription itself, acting in cis, represses Ubx. The Trithorax complex TAC1 binds the Ubx coding region in nuclei expressing Ubx, and the bxd region in nuclei not expressing Ubx. We propose that TAC1 promotes the mosaic pattern of Ubx expression by facilitating transcriptional elongation of bxd ncRNAs, which represses Ubx transcription.

Comparing active and repressed expression states of genes controlled by the Polycomb/Trithorax group proteins

“…The transcription of noncoding RNAs (ncRNAs) seem to play an important, although diverse, role in the regulation of the BX-C. Petruk et al (42,43) found that noncoding transcription through the bxd PRE is crucial for Ubx repression and that transcription through Mcp overlaps with AbdB transcription in the embryo. Work from others and our laboratory showing that ncRNA transcription in the AbdB domain coincides with an active AbdB gene indicates a nonuniversal, gene specific function for ncRNAs in the BX-C (31,43,44).…”

“…Trx-and TAC1-interacting histone acetyltransferases may then be responsible for setting epigenetic marks that maintain the active transcription state. Petruk et al (42) showed that Trx is required for transcription elongation and that it is localized in the gene body of active Ubx, caused by the interaction with elongation factors. In contrast, Papp and Muller (16), who investigated the distribution of PcG and TrxG proteins at the active and repressed Ubx gene in imaginal discs, found the same restricted Trx profile as we did, namely Trx binding at discrete sites.…”

New meaning in the message: Noncoding RNAs and their role in retinal development

“…It has been suggested that bxd acts in trans to recruit histone methyltransferases to Ubx enhancer elements and thus promotes stable activation of transcription (SanchezElsner et al, 2006). Other groups, however, have claimed that bxd has no effect in trans, but instead acts in cis via transcriptional interference to prevent recruitment of trithorax proteins to the enhancer elements, and thus represses expression of Ubx (Petruk et al, 2006).…”

Epigenetics in development

“…NURF facilitates active chromatin by repositioning nucleosomes along DNA (Sims and Reinberg, 2006). TrxG also promotes expression of the Hox gene Ubx by facilitating transcriptional elongation (Petruk et al, 2006). These findings may explain how trxG regulates gene activation.…”