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:

• Yayli G., Bernardini A., Mendoza Sanchez P.K., Scheer E., Damilot M., Essabri K., Morlet B., Negroni L., Vincent S.D., Timmers H.T.M. and Tora L. (2023) ATAC and SAGA co-activator complexes utilize co-translational assembly, but their cellular localization properties and functions are distinct. Cell Rep 42, 113099.
• Fotouhi O., Nizamuddin S., Falk S., Schilling O., Knüchel-Clarke R., Biniossek M.L. and Timmers H.T.M. (2023) Alternative mRNA Splicing Controls the Functions of the Histone H3K27 Demethylase UTX/KDM6A. Cancers (Basel) 15,
 doi 10.3390/cancers15123117.
• Bernardini A., Mukherjee P., Scheer E., Kamenova I., Antonova S., Mendoza Sanchez P.K., Yayli G., Morlet B., Timmers H.T.M. and Tora L. (2023) Hierarchical TAF1-dependent co-translational assembly of the basal transcription factor TFIID. Nat Struct Mol Biol 30, 1141-1152.
• Dreijerink K.M.A., Ozyerli-Goknar E., Koidl S., Van Der Lelij E.J., Van Den Heuvel P., Kooijman J.J., Biniossek M.L., Rodenburg K.W., Nizamuddin S. and Timmers H.T.M. (2022) Multi-omics analyses of MEN1 missense mutations identify disruption of menin-MLL and menin-JunD interactions as critical requirements for molecular pathogenicity. Epigenetics Chromatin 15, 29.
• Capponi S., Stöffler N., Penney E.B., Grütz K., Nizamuddin S., Vermunt M.W., Castelijns B., Fernandez-Cerado C., Legarda G.P., Velasco-Andrada M.S., Muñoz E.L., Ang M.A., Diesta C.C.E., Creyghton M.P., Klein C., Bragg D.C., De Rijk P. and Timmers H.T.M. (2021) Dissection of TAF1 neuronal splicing and implications for neurodegeneration in X-linked dystonia-parkinsonism. Brain Commun 3, fcab253.
• 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.