Dominant and redundant functions of TFIID involved in the regulation of hepatic genes.
To study the in vivo role of TFIID in the transcriptional regulation of hepatic genes, we generated mice with liver-specific disruption of the TAF10 gene. Inactivation of TAF10 in hepatocytes resulted in the dissociation of TFIID into individual components. This correlated with the downregulation of most hepatocyte-specific genes during embryonic life and a defect in liver organogenesis. Unexpectedly, however, the transcription of less than 5% of active genes was affected by TAF10 inactivation and TFIID disassembly in adult liver. The extent of changes in transcription of the affected genes was dependent on the timing of their activation during liver development, relative to that of TAF10 inactivation. Furthermore, TFIID dissociation from promoters leads to the re-expression of several postnatally silenced hepatic genes. Promoter occupancy analyses, combined with expression profiling, demonstrate that TFIID is required for the initial activation or postnatal repression of genes, while it is dispensable for maintaining ongoing transcription.
Tatarakis
Antonis
A
Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece.
Margaritis
Thanasis
T
Institute of Molecular Biology and Biotechnology, FORTH, Herakleion 71110, Greece.
Martinez-Jimenez
Celia Pilar
CP
Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece.
Kouskouti
Antigone
A
Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece.
Mohan
William S
WS
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, 1 Rue Laurent Fries, 67404 Illkirch, France.
Haroniti
Anna
A
Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece.
Kafetzopoulos
Dimitris
D
Institute of Molecular Biology and Biotechnology, FORTH, Herakleion 71110, Greece.
Tora
Làszlò
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104, 1 Rue Laurent Fries, 67404 Illkirch, France.
Talianidis
Iannis
I
Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece. Electronic address: talianidis@fleming.gr.
D000818:Animals; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009928:Organ Specificity; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D021122:Protein Subunits; D012333:RNA, Messenger; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D012319:RNA Polymerase II