Differentiation Driven Changes in the Dynamic Organization of Basal Transcription Initiation

 

Giuseppina Giglia-Mari1,2,3*, Arjan F. Theil1#, Pierre-Olivier Mari1,2,3#, Sophie Mourgues2,3, Julie Nonnekens1, Lise O. Andrieux1, Jan de Wit1, Catherine Miquel1, Nils Wijgers1, Alex Maas1, Maria Fousteri4, Jan H. J. Hoeijmakers1, Wim Vermeulen1

 

1 Department of Genetics, Erasmus MC, Rotterdam, The Netherlands,
2 CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France,
3 Université de Toulouse, UPS, IPBS, Toulouse, France,
4 Department of Toxicogenetics, LUMC, Leiden, The Netherlands

 

CORRESPONDENCEE-mail: ambra.mari@ipbs.fr (GG-M); w.vermeulen@erasmusmc.nl (WV)

 

Abstract

Studies based on cell-free systems and on in vitro–cultured living cells support the concept that many cellular processes, such as transcription initiation, are highly dynamic: individual proteins stochastically bind to their substrates and disassemble after reaction completion.

This dynamic nature allows quick adaptation of transcription to changing conditions. However, it is unknown to what extent this dynamic transcription organization holds for postmitotic cells embedded in mammalian tissue. To allow analysis of transcription initiation dynamics directly into living mammalian tissues, we created a knock-in mouse model expressing fluorescently tagged TFIIH.

Surprisingly and in contrast to what has been observed in cultured and proliferating cells, postmitotic murine cells embedded in their tissue exhibit a strong and long-lasting transcription-dependent immobilization of TFIIH. This immobilization is both differentiation driven and development dependent.

Furthermore, although very statically bound, TFIIH can be remobilized to respond to new transcriptional needs.

This divergent spatiotemporal transcriptional organization in different cells of the soma revisits the generally accepted highly dynamic concept of the kinetic framework of transcription and shows how basic processes, such as transcription, can be organized in a fundamentally different fashion in intact organisms as previously deduced from in vitro studies.