Noncoding RNAs of Trithorax Response Elements Recruit Drosophila Ash1 to Ultrabithorax

Abstract

Homeotic genes contain cis-regulatory trithorax response elements (TREs) that are targeted by epigenetic activators and transcribed in a tissue-specific manner. We show that the transcripts of three TREs located in the Drosophila homeotic gene Ultrabithorax (Ubx) mediate transcription activation by recruiting the epigenetic regulator Ash1 to the template TREs. TRE transcription coincides with Ubx transcription and recruitment of Ash1 to TREs in Drosophila. The SET domain of Ash1 binds all three TRE transcripts, with each TRE transcript hybridizing with and recruiting Ash1 only to the corresponding TRE in chromatin. Transgenic transcription of TRE transcripts restores recruitment of Ash1 to Ubx TREs and restores Ubx expression in Drosophila cells and tissues that lack endogenous TRE transcripts. Small interfering RNA-induced degradation of TRE transcripts attenuates Ash1 recruitment to TREs and Ubx expression, which suggests that noncoding TRE transcripts play an important role in epigenetic activation of gene expression.

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

“…Therefore, intergenic transcripts derived from the TRE locus mediate the recruitment of Ash1 to the TRE DNA elements of Ubx. These ncRNA transcripts serve as an intermediary between the TRE DNA elements and Ash1 protein (Sanchez-Elsner et al 2006). These data further support a model in which an intergenic ncRNA transcribed from the TRE of Ubx is retained at the TRE through DNA-RNA interactions and plays an important role in providing an RNA scaffold that is recognized by Ash1.…”

“…The early transcripts (1.1-1.3 kb, are processed from a 26-kb precursor) appear to be ncRNAs, whereas the late transcripts (0.8 kb) can be translated to produce a protein (Lipshitz et al 1987). Recently, an elegant study by Sauer and colleagues (Sanchez-Elsner et al 2006) provided direct evidence of the role of intergenic transcripts from the Ubx region in epigenetic activation of gene expression. The Ubx locus contains multiple cis-regulatory elements known as trithorax response elements (TRE) that recruit transcriptional activators such as the trithorax group (trxG) of epigenetic regulators.…”

“…It has previously been shown that intergenic transcription of ncRNAs from TRE/PRE elements switches a silent PRE to a TRE, which indicates that TRE/PRE transcription plays an important role in epigenetic activation (Lipshitz et al 1987;Rank et al 2002;Schmitt et al 2005). Recent studies by Sanchez-Elsner (Sanchez-Elsner et al 2006) further showed that these intergenic transcripts from the TRE at the Ubx locus mediate transcriptional activation of Ubx by recruiting the epigenetic regulator Ash1 to the TRE elements. Ash1 is a histone methyltransferase (HMT) that promotes transcriptional activation by trimethylating H3K4, H3K9, and H4K20 (Beisel et al 2002) and is essential for the tissue-specific expression of Ubx (Beisel et al 2002 and references therein).…”

Epigenetics in development

“…Acti-vation of PRE/TRE requires transcription of the TRE. Noncoding TRE transcripts bind and recruit the Drosophila trxG HMT Ash1, which deposits marks for euchromatin, H3K4me3 (Sanchez-Elsner et al, 2006). Recent studies show that BPTF specifically binds H3K4me3, and loss of Xenopus BPTF results in aberrant Hox expression.…”

The activatory long non-coding RNA DBE-T reveals the epigenetic etiology of facioscapulohumeral muscular dystrophy

“…Moreover, its expression is correlated with lower MyoD expression levels, preventing normal cell signaling, and contributing to the final FSHD phenotype [8]. In particular, DBE-T interacts with one of the Trx components, the ASH1L protein, which has also been studied in Drosophila, demonstrating its involvement in the activation of Hox gene expression when it is recruited to Hox regulatory elements by lncRNAs [9]. Wang et al [10] described the first activatory lncRNA in 2011: HOTTIP, a long intergenic non-coding RNA (lincRNA) involved in the production of HOXA genes.…”