The H1 and H2 regions of the activation domain of herpes simplex virion protein 16 stimulate transcription through distinct molecular mechanisms.
BACKGROUND
The Herpes Simplex Virion Protein 16 (VP16) contains a strong activation domain which can be subdivided into two regions, H1 and H2, both of which independently activate transcription in vivo. Several components of the basal transcription machinery have been shown to interact with the activation domain of VP16, mostly through the H1 region.


RESULTS
We show that the H2 region binds directly to histone acetyltransferase, CBP (CREB (cAMP Responsive Element Binding Protein) Binding Protein) both in vivo and in vitro. The sites of interaction with the H2 region were mapped to both the amino- and carboxy-terminal segments of CBP. A mutation in the H2 region disrupts the interaction with CBP and abolishes the ability of VP16 to mediate in vitro transactivation from chromatin templates in an acetyl-CoA dependent manner. In contrast, human Mediator, another co-activator complex, binds specifically to both the H1 and H2 regions.


CONCLUSIONS
The H1 and H2 regions of the VP16 activation domain activate transcription via distinct pathways. The H2 requires CBP for activation, whereas the H1 may function through Mediator and general transcription factors.
Ikeda
Keiko
K
Department of Biology, Jichi Medical School, Minamikawachi-machi, Kawachi, Tochigi 329-0498, Japan. kikeda@jichi.ac.jp
Stuehler
Thomas
T
Meisterernst
Michael
M
D001665:Binding Sites; D050882:CREB-Binding Protein; D004926:Escherichia coli; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D017405:Herpes Simplex Virus Protein Vmw65; D009687:Nuclear Proteins; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D005982:Glutathione Transferase