Differentiation driven changes in the dynamic organization of Basal transcription initiation.
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.
Giglia-Mari
Giuseppina
G
Department of Genetics, Erasmus MC, Rotterdam, The Netherlands. ambra.mari@ipbs.fr
Theil
Arjan F
AF
Mari
Pierre-Olivier
PO
Mourgues
Sophie
S
Nonnekens
Julie
J
Andrieux
Lise O
LO
de Wit
Jan
J
Miquel
Catherine
C
Wijgers
Nils
N
Maas
Alex
A
Fousteri
Maria
M
Hoeijmakers
Jan H J
JH
Vermeulen
Wim
W
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D036681:Fluorescence Recovery After Photobleaching; D018507:Gene Expression Regulation, Developmental; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D051758:Transcription Factor TFIIH