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Dominant and redundant functions of TFIID involved in the regulation of hepatic genes.
- Source :
-
Molecular cell [Mol Cell] 2008 Aug 22; Vol. 31 (4), pp. 531-543. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Animals
Gene Expression Profiling
Gene Targeting
Hepatocytes cytology
Hepatocytes metabolism
Liver embryology
Mice
Mice, Knockout
Models, Genetic
Organ Specificity
Phenotype
Promoter Regions, Genetic genetics
Protein Binding
Protein Subunits metabolism
RNA Polymerase II metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Transcription Factors metabolism
Transcription, Genetic
Gene Expression Regulation, Developmental
Liver metabolism
Transcription Factor TFIID metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 31
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 18722179
- Full Text :
- https://doi.org/10.1016/j.molcel.2008.07.013