Signal-specific co-activator domain requirements for Pit-1 activation.
POU-domain proteins, such as the pituitary-specific factor Pit-1, are members of the homeodomain family of proteins which are important in development and homeostasis, acting constitutively or in response to signal-transduction pathways to either repress or activate the expression of specific genes. Here we show that whereas homeodomain-containing repressors such as Rpx2 seem to recruit only a co-repressor complex, the activity of Pit-1 is determined by a regulated balance between a co-repressor complex that contains N-CoR/SMRT, mSin3A/B and histone deacetylases, and a co-activator complex that includes the CREB-binding protein (CBP) and p/CAF. Activation of Pit-1 by cyclic AMP or growth factors depends on distinct amino- and carboxy-terminal domains of CBP, respectively. Furthermore, the histone acetyltransferase functions of CBP or p/CAF are required for Pit-1 function that is stimulated by cyclic AMP or growth factors, respectively. These data show that there is a switch in specific requirements for histone acetyltransferases and CBP domains in mediating the effects of different signal-transduction pathways on specific DNA-bound transcription factors.
Xu
L
L
Howard Hughes Medical Institute, University of California at San Diego, La Jolla 92093-0648, USA.
Lavinsky
R M
RM
Dasen
J S
JS
Flynn
S E
SE
McInerney
E M
EM
Mullen
T M
TM
Heinzel
T
T
Szeto
D
D
Korzus
E
E
Kurokawa
R
R
Aggarwal
A K
AK
Rose
D W
DW
Glass
C K
CK
Rosenfeld
M G
MG
D000123:Acetyltransferases / Q000378:metabolism; D001667:Binding, Competitive; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1; D010766:Phosphorylation; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D000242:Cyclic AMP; D004268:DNA-Binding Proteins; D006133:Growth Substances; D051548:Histone Acetyltransferases; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C539127:NCOR1 protein, human; C494187:POU1F1 protein, human; C494363:CREBBP protein, human