Mitotic regulation of TFIID: inhibition of activator-dependent transcription and changes in subcellular localization.
Mitosis in higher eukaryotes is accompanied by a general inhibition of transcription. To begin to understand the mechanisms underlying this inhibition we have examined the behavior of the general transcription factor TFIID during mitosis. Immunocytochemistry and subcellular fractionation studies indicate that the majority of TFIID is displaced from the disassembling prophase nucleus to the mitotic cytoplasm around the time of nuclear envelope breakdown. However, a subpopulation of TFIID remains associated tightly with the condensed mitotic chromosomes. Metabolic labeling of mitotic cells revealed that several subunits of TFIID undergo mitosis-specific phosphorylation, but in spite of these changes, the TFIID complex remains intact. Functional analysis of purified TFIID from mitotic cells shows that phosphorylated forms are unable to direct activator-dependent transcription, but that this activity is restored upon dephosphorylation. These results demonstrate that TFIID regulation by phosphorylation is likely to have an important role in mitotic inhibition of RNA polymerase II transcription. In addition, they suggest a mechanism for regulating gene expression through the selective disruption of polymerase II promoter structures during mitosis.
Segil
N
N
Laboratory of Molecular Biology, Rockefeller University, New York 10021, USA.
Guermah
M
M
Hoffmann
A
A
Roeder
R G
RG
Heintz
N
N
D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry; D002875:Chromosomes / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011418:Prophase / Q000502:physiology; D012319:RNA Polymerase II; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000032:analysis / Q000502:physiology*; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000032:analysis* / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D012319:RNA Polymerase II; D010744:Phosphoric Monoester Hydrolases