Nuclear structure-associated TIF2 recruits glucocorticoid receptor and its target DNA.
Assembly of multi-protein complexes on promoter and enhancer elements is a prerequisite for onset of gene transcription. At the beginning of this process, transcription factors are thought to act as nucleating centers for complex formation through the binding of their target DNA sequences, and thereafter recruit coactivators. Here, we investigated this process of assembly by determining the distribution of the glucocorticoid receptor (GR) and its coactivator, TIF2. Both endogenously and ectopically expressed TIF2 were shown to form foci in the nucleus, and GR could be recruited to the TIF2 foci upon GR agonist but not antagonist treatment. Moreover, we show that the coactivators, p300 and PCAF, are also recruited to the TIF2 foci. The TIF2 foci could recruit GR carrying a microinjected GR responsive element. We propose that TIF2 provides a nuclear compartment that allows the assembly of multi-protein complexes required for GR-mediated gene activation.
Ogawa
Hidesato
H
Department of Biochemistry, Institute for Virus Research, Kyoto University, Japan. hidesato@nibb.ac.jp
Yu
Ruth T
RT
Haraguchi
Tokuko
T
Hiraoka
Yasushi
Y
Nakatani
Yoshihiro
Y
Morohashi
Ken-ichirou
K
Umesono
Kazuhiko
K
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D022003:Cell Nucleus Structures / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D018091:Receptors, AMPA / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D002352:Carrier Proteins; C491310:GRIP1 protein, human; C498001:NCOA2 protein, human; D009419:Nerve Tissue Proteins; D051958:Nuclear Receptor Coactivator 2; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D004247:DNA