The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription. (4th September 2017) - Zouaz, Amel
Abstract: In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Drosophila Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter‐proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature. We found that AbdA binding to M1BP‐regulated genes results in reduction in PcG binding, the release of paused Pol II, increases in promoter H3K4me3 histone marks and increased gene transcription. Linking transcription factors, PcG proteins and paused Pol II states, these data identify a two‐step mechanism of Hox‐driven transcription, with M1BP binding leading to Pol II recruitment followed by AbdA targeting, which results in a change in the chromatin landscape and enhanced transcription. Synopsis: Interaction between Hox proteins and a transcription pause factor stimulates formation of active chromatin marks at target promoters and drives RNA pol II into productive elongation, showing that transcription factors not only control polymerase recruitment but also stimulate transition from paused to productive Pol II. The Drosophila Hox proteins AbdA and Ubx interact with the transcription factor M1BP. M1BP activity is required in Hox‐controlled processes in Drosophila . AbdA and Ubx target M1BP‐controlled proximal promoters enriched with PcG proteins and displaying paused RNA Polymerase II. Promoter‐proximal binding of AbdA at M1BP‐controlled genes leads to loss of PcG binding, increased H3K4me3 histone marks, release of paused RNA Polymerase II and increased transcription. Abstract : Hox protein binding to target genes bearing paused polymerase triggers the formation of active chromatin marks and drives RNA pol II into productive elongation.