Epigenetic regulation of TFIID recruitment and activity


Project Summary

Epigenetic control of chromatin states is tightly linked to the transcriptional programmes of cells. The basal transcription factor TFIID acts at the crossroads between gene activation signals and RNA polymerase II transcription machinery. We aim to dissect the contributions of histone modifications and chromatin binding dynamics to the function of human promoters. The results of our study will provide a detailed understanding of the epigenetic mechanisms controlling gene transcription and differentiation in mammalian cells.

Selected project-relevant publications:

  • Timmers H.T.M. (2020) SAGA and TFIID: Friends of TBP drifting apart. Biochim Biophys Acta Gene Regul Mech 194604, doi: 10.1016/j.bbagrm.2020.194604.
  • Frew I.J., Timmers H.T.M., Schüle R. and Gratzke C. (2020) The complex genetics of epigenetics in urothelial carcinomas. Nat Rev Urol, doi: 10.1038/s41585-41020-00386-41585.
  • Capponi S., Stöffler N., Irimia M., Van Schaik F.M.A., Ondik M.M., Biniossek M.L., Lehmann L., Mitschke J., Vermunt M.W., Creyghton M.P., Graybiel A.M., Reinheckel T., Schilling O., Blencowe B.J., Crittenden J.R. and Timmers H.T.M. (2020) Neuronal-specific microexon splicing of TAF1 mRNA is directly regulated by SRRM4/nSR100. RNA Biol 17, 62-74.
  • Kamenova I., Mukherjee P., Conic S., Mueller F., El-Saafin F., Bardot P., Garnier J.M., Dembele D., Capponi S., Timmers H.T.M., Vincent S.D. and Tora L. (2019) Co-translational assembly of mammalian nuclear multisubunit complexes. Nat Commun 10, 1740.
  • Bhuiyan T. and Timmers H.T.M. (2019) Promoter Recognition: Putting TFIID on the Spot. Trends Cell Biol 29, 752-763.
  • Antonova S.V., Boeren J., Timmers H.T.M. and Snel B. (2019) Epigenetics and transcription regulation during eukaryotic diversification: the saga of TFIID. Genes Dev 33, 888-902.
  • Timmers H.T.M. and Tora L. (2018) Transcript Buffering: A Balancing Act between mRNA Synthesis and mRNA Degradation. Mol Cell 72, 10-17.
  • Antonova S.V., Haffke M., Corradini E., Mikuciunas M., Low T.Y., Signor L., Van Es R.M., Gupta K., Scheer E., Vos H.R., Tora L., Heck A.J.R., Timmers H.T.M. and Berger I. (2018) Chaperonin CCT checkpoint function in basal transcription factor TFIID assembly. Nat Struct Mol Biol 25, 1119-1127.
  • Timmers H.T. and Verrijzer C.P. (2017) Mitotic Chromosomes: Not So Silent After All. Dev Cell 43, 119-121.
  • Koster M.J., Snel B. and Timmers H.T. (2015) Genesis of chromatin and transcription dynamics in the origin of species. Cell 161, 724-736.
  • Dreijerink K.M., Conemans E.B, Cornelissen C., van Blokland M.T., Mannstadt M., Pieterman C.R., Binquet C., Dekkers O.M., Drent M.L., Horst-Schrivers A.N., de Herder W.W., Havekes B., Fliers E., Vriens M.R., Timmers H.T., van der Wall E., Brown M., van der Luijt R.B., van Diest P.J., Goudet P., Burgess J.R. and Valk G.D. (2014) Breast-cancer predisposition in multiple endocrine neoplasia type 1. N Engl J Med 371, 583-584.
  • Pijnappel W.W., Esch D., Baltissen M.P., Wu G., Mischerikow N., Bergsma A.J., Van Der Wal E., Han D.W., Bruch H., Moritz S., Lijnzaad P., Altelaar A.F., Sameith K., Zaehres H., Heck A.J., Holstege F.C., Scholer H.R. and Timmers H.T. (2013) A central role for TFIID in the pluripotent transcription circuitry. Nature 495, 516-519.