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 fract ionation studies indicate that the majority of TFIID is displaced from the disassembling prophase nucleus to the mitotic cytoplasm around th e time of nuclear envelope breakdown. However, a subpopulation of TFII D remains associated tightly with the condensed mitotic chromosomes. M etabolic labeling of mitotic cells revealed that several subunits of T FIID undergo mitosis-specific phosphorylation, but in spite of these c hanges, the TFIID complex remains intact. Functional analysis of purif ied TFIID from mitotic cells shows that phosphorylated forms are unabl e to direct activator-dependent transcription, but that this activity is restored upon dephosphorylation. These results demonstrate that TFI ID regulation by phosphorylation is likely to have an important role i n mitotic inhibition of RNA polymerase II transcription. In addition, they suggest a mechanism for regulating gene expression through the se lective disruption of polymerase II promoter structures during mitosis .