Chaperoning RNA Polymerase II through repressive chromatin

Abstract

EMBO J (2013) 32: 1075–1086 doi:; DOI: 10.1038/emboj.2013.54; published online March 15 2013

The histone chaperone Spt6 is known to facilitate transcriptional elongation while preventing spurious initiation of transcription within the coding region of genes. A recent publication in The EMBO Journal (Wang et al, 2013) identifies an additional mechanism by which Spt6 promotes gene expression by demonstrating that it tethers the histone demethylase UTX/KDM6A to the elongating RNA Polymerase II, thereby enabling the removal of repressive H3K27me3 marks within developmentally important muscle genes.

Figure 1

Spt6 enhances transcriptional elongation by tethering UTX/KDM6A to RNA Pol II. Wang et al (2013) demonstrate that Spt6 is essential for the expression of developmentally regulated muscle genes, as it tethers the histone demethylase UTX (KDM6A) to the elongating polymerase to ensure efficient removal of repressive H3K27me3 marks. Concurrent with the removal of H3K27me3, Spt6 is also required for accumulation of SetD2-mediated H3K36me3 marks within the gene body. As H3K36me3 has been shown to act as a docking site for the PCL1/3 components of the PRC2 complex, a temporary condensing of nucleosomes through a transient H3K27me3 mark could be envisaged. This repressive mark would then be quickly removed upon the arrival of the queued elongating RNA Pol II molecules traversing the gene. Therefore, Spt6 may modulate an on-going antagonism between UTX and PRC2 in the gene body to ensure efficient transcriptional elongation of transcripts initiated from the gene promoter, while preventing spurious transcription from initiating at cryptic sites within the gene.