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Development 2016 Apr 15;1438:1340-50. doi: 10.1242/dev.127936.
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Activation of a T-box-Otx2-Gsc gene network independent of TBP and TBP-related factors.

Gazdag E , Jacobi UG , van Kruijsbergen I , Weeks DL , Veenstra GJ .

Embryonic development relies on activating and repressing regulatory influences that are faithfully integrated at the core promoter of individual genes. In vertebrates, the basal machinery recognizing the core promoter includes TATA-binding protein (TBP) and two TBP-related factors. In Xenopus embryos, the three TBP family factors are all essential for development and are required for expression of distinct subsets of genes. Here, we report on a non-canonical TBP family-insensitive (TFI) mechanism of transcription initiation that involves mesoderm and organizer gene expression. Using TBP family single- and triple-knockdown experiments, α-amanitin treatment, transcriptome profiling and chromatin immunoprecipitation, we found that TFI gene expression cannot be explained by functional redundancy, is supported by active transcription and shows normal recruitment of the initiating form of RNA polymerase II to the promoter. Strikingly, recruitment of Gcn5 (also known as Kat2a), a co-activator that has been implicated in transcription initiation, to TFI gene promoters is increased upon depletion of TBP family factors. TFI genes are part of a densely connected TBP family-insensitive T-box-Otx2-Gsc interaction network. The results indicate that this network of genes bound by Vegt, Eomes, Otx2 and Gsc utilizes a novel, flexible and non-canonical mechanism of transcription that does not require TBP or TBP-related factors.

PubMed ID: 26952988
PMC ID: PMC4852510
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: bmp4 crx eomes fgf8 foxd3 gsc h3-3a h4c1 kat2a lhx1 mark3 nodal nodal1 not otx2 rhob taf6 tbp tbpl1 tbpl2 vegt zic1
Antibodies: Acetylated H3f3a Ab15 Acetylated Hist1h4a Ab6 Kat2a Ab1 Kat2a Ab2 Polr2a Ab2 Polr2a Ab6 Tbp Ab1

GEO Series: GSE76991: Xenbase,  NCBI
GSE76994: Xenbase,  NCBI
GSE76995: NCBI

Article Images: [+] show captions
References [+] :
Adelman, Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. 2012, Pubmed