Recent work has shown that RNA polymerase (Pol) II can be recruited to and transcribe distal regulatory regions. Here we analyzed transcription initiation and elongation through genome-wide localization of Pol II, general transcription factors (GTFs) and active chromatin in developing T cells. We show that Pol II and GTFs are recruited to known T cell–specific enhancers. We extend this observation to many new putative enhancers, a majority of which can be transcribed with or without polyadenylation. Importantly, we also identify genomic features called transcriptional initiation platforms (TIPs) that are characterized by large areas of Pol II and GTF recruitment at promoters, intergenic and intragenic regions. TIPs show variable widths (0.4–10 kb) and correlate with high CpG content and increased tissue specificity at promoters. Finally, we also report differential recruitment of TFIID and other GTFs at promoters and enhancers. Overall, we propose that TIPs represent important new regulatory hallmarks of the genome.
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Work in the P.F. laboratory is supported by institutional grants from Institut National de la Santé et de la Recherche Médicale and the Centre National de la Recherche Scientifique (CNRS), and by specific grants from the Fondation Princesse Grace de Monaco, the Agence Nationale de la Recherche (ANR), the Institut National du Cancer (INCa) and the Commission of the European Communities. F.K. was supported by grants from Chromatin Plasticity, Marie Curie Research Training Network and Association pour la Recherche sur le Cancer, R.F. by Genopole and CNRS, and P.C. by grants from INCa and Fondation pour la Recherche Médicale. The work was also supported by a Regulome grant from the ANR. D.E. was supported by Deutsche Forschungsgemeinschaft, Transregio-5. We are grateful to B. Escaliere for useful advice on the statistical analyses, to J.J. Waterfall and J.L. Core from the Lis lab (Cornell University, Ithaca, USA) for help in the generation of the mappability track, to G. Natoli (European Institute of Oncology) for the gift of plasmids used in preliminary experiments for reporter assays, to E. Soucie and V. Cauchy for critical reading of the manuscript, to J. Blanc for technical assistance, to Y. Duffourd from the Centre National de Génotypage-Commissariat à l'Energie Atomique lab for sequencing quality controls and to members of the P.F. lab for help and advice. We dedicate this work to the memory of distinguished colleague Vanessa Ranc-Rongere, who left us too early.
The authors declare no competing financial interests.
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Koch, F., Fenouil, R., Gut, M. et al. Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nat Struct Mol Biol 18, 956–963 (2011). https://doi.org/10.1038/nsmb.2085
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