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.
Department of Genetics, Erasmus MC, Rotterdam, The Netherlands. ambra.mari@ipbs.fr
Giuseppina
G
Giglia-Mari
Arjan F
AF
Theil
Pierre-Olivier
PO
Mari
Sophie
S
Mourgues
Julie
J
Nonnekens
Lise O
LO
Andrieux
Jan
J
de Wit
Catherine
C
Miquel
Nils
N
Wijgers
Alex
A
Maas
Maria
M
Fousteri
Jan H J
JH
Hoeijmakers
Wim
W
Vermeulen
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