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. 1996 Jun;16(6):2967–2976. doi: 10.1128/mcb.16.6.2967

Differential control of transcription by homologous homeodomain coregulators.

C C Huang 1, W Herr 1
PMCID: PMC231291  PMID: 8649408

Abstract

The human herpes simplex virus type 1 (HSV-1) transactivator VP16 and its homolog from bovine herpes-virus 1 (BHV-1) can each recruit the human homeodomain protein Oct-1 into a transcriptional regulatory complex. Here, we show that these two Oct-1 coregulators possess similar, if not identical, homeodomain recognition properties but possess different virus-specific cis-regulatory specificities: the HSV-1 VP-16 protein activates transcription from the HSV-1 VP16 response element, and the BHV-1 VP16 protein activates transcription from the BHV-1 VP16 response element. A distinct 3-bp segment, the D segment, lying 3' of the canonical TAATGARAT motif (where R is a purine) in the VP16 response element is responsible for the differential cis element recognition and transcriptional activation by these two homeodomain coregulators. These results demonstrate how a single homeodomain protein can direct differential transcriptional regulation by selective association with homologous homeodomain coregulators.

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Selected References

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  1. Aurora R., Herr W. Segments of the POU domain influence one another's DNA-binding specificity. Mol Cell Biol. 1992 Feb;12(2):455–467. doi: 10.1128/mcb.12.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carpenter D. E., Misra V. Sequences of the bovine herpesvirus 1 homologue of herpes simplex virus type-1 alpha-trans-inducing factor (UL48). Gene. 1992 Oct 1;119(2):259–263. doi: 10.1016/0378-1119(92)90280-3. [DOI] [PubMed] [Google Scholar]
  3. Cleary M. A., Herr W. Mechanisms for flexibility in DNA sequence recognition and VP16-induced complex formation by the Oct-1 POU domain. Mol Cell Biol. 1995 Apr;15(4):2090–2100. doi: 10.1128/mcb.15.4.2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleary M. A., Stern S., Tanaka M., Herr W. Differential positive control by Oct-1 and Oct-2: activation of a transcriptionally silent motif through Oct-1 and VP16 corecruitment. Genes Dev. 1993 Jan;7(1):72–83. doi: 10.1101/gad.7.1.72. [DOI] [PubMed] [Google Scholar]
  5. Das G., Hinkley C. S., Herr W. Basal promoter elements as a selective determinant of transcriptional activator function. Nature. 1995 Apr 13;374(6523):657–660. doi: 10.1038/374657a0. [DOI] [PubMed] [Google Scholar]
  6. Elliott G. D. The extreme carboxyl terminus of the equine herpesvirus 1 homolog of herpes simplex virus VP16 is essential for immediate-early gene activation. J Virol. 1994 Aug;68(8):4890–4897. doi: 10.1128/jvi.68.8.4890-4897.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gerster T., Roeder R. G. A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347–6351. doi: 10.1073/pnas.85.17.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goutte C., Johnson A. D. a1 protein alters the DNA binding specificity of alpha 2 repressor. Cell. 1988 Mar 25;52(6):875–882. doi: 10.1016/0092-8674(88)90429-1. [DOI] [PubMed] [Google Scholar]
  9. Herr W., Cleary M. A. The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev. 1995 Jul 15;9(14):1679–1693. doi: 10.1101/gad.9.14.1679. [DOI] [PubMed] [Google Scholar]
  10. Keleher C. A., Goutte C., Johnson A. D. The yeast cell-type-specific repressor alpha 2 acts cooperatively with a non-cell-type-specific protein. Cell. 1988 Jun 17;53(6):927–936. doi: 10.1016/s0092-8674(88)90449-7. [DOI] [PubMed] [Google Scholar]
  11. Keleher C. A., Passmore S., Johnson A. D. Yeast repressor alpha 2 binds to its operator cooperatively with yeast protein Mcm1. Mol Cell Biol. 1989 Nov;9(11):5228–5230. doi: 10.1128/mcb.9.11.5228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kristie T. M., LeBowitz J. H., Sharp P. A. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. EMBO J. 1989 Dec 20;8(13):4229–4238. doi: 10.1002/j.1460-2075.1989.tb08608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kristie T. M., Sharp P. A. Interactions of the Oct-1 POU subdomains with specific DNA sequences and with the HSV alpha-trans-activator protein. Genes Dev. 1990 Dec;4(12B):2383–2396. doi: 10.1101/gad.4.12b.2383. [DOI] [PubMed] [Google Scholar]
  14. Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
  15. Lai J. S., Cleary M. A., Herr W. A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev. 1992 Nov;6(11):2058–2065. doi: 10.1101/gad.6.11.2058. [DOI] [PubMed] [Google Scholar]
  16. Lai J. S., Herr W. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958–6962. doi: 10.1073/pnas.89.15.6958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Misra V., Bratanich A. C., Carpenter D., O'Hare P. Protein and DNA elements involved in transactivation of the promoter of the bovine herpesvirus (BHV) 1 IE-1 transcription unit by the BHV alpha gene trans-inducing factor. J Virol. 1994 Aug;68(8):4898–4909. doi: 10.1128/jvi.68.8.4898-4909.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moriuchi H., Moriuchi M., Cohen J. I. Proteins and cis-acting elements associated with transactivation of the varicella-zoster virus (VZV) immediate-early gene 62 promoter by VZV open reading frame 10 protein. J Virol. 1995 Aug;69(8):4693–4701. doi: 10.1128/jvi.69.8.4693-4701.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Moriuchi H., Moriuchi M., Straus S. E., Cohen J. I. Varicella-zoster virus open reading frame 10 protein, the herpes simplex virus VP16 homolog, transactivates herpesvirus immediate-early gene promoters. J Virol. 1993 May;67(5):2739–2746. doi: 10.1128/jvi.67.5.2739-2746.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. O'Hare P., Goding C. R., Haigh A. Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. EMBO J. 1988 Dec 20;7(13):4231–4238. doi: 10.1002/j.1460-2075.1988.tb03320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pomerantz J. L., Kristie T. M., Sharp P. A. Recognition of the surface of a homeo domain protein. Genes Dev. 1992 Nov;6(11):2047–2057. doi: 10.1101/gad.6.11.2047. [DOI] [PubMed] [Google Scholar]
  22. Pomerantz J. L., Pabo C. O., Sharp P. A. Analysis of homeodomain function by structure-based design of a transcription factor. Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9752–9756. doi: 10.1073/pnas.92.21.9752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Purewal A. S., Allsopp R., Riggio M., Telford E. A., Azam S., Davison A. J., Edington N. Equid herpesviruses 1 and 4 encode functional homologs of the herpes simplex virus type 1 virion transactivator protein, VP16. Virology. 1994 Jan;198(1):385–389. doi: 10.1006/viro.1994.1047. [DOI] [PubMed] [Google Scholar]
  24. Stark M. R., Johnson A. D. Interaction between two homeodomain proteins is specified by a short C-terminal tail. Nature. 1994 Sep 29;371(6496):429–432. doi: 10.1038/371429a0. [DOI] [PubMed] [Google Scholar]
  25. Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
  26. Stern S., Herr W. The herpes simplex virus trans-activator VP16 recognizes the Oct-1 homeo domain: evidence for a homeo domain recognition subdomain. Genes Dev. 1991 Dec;5(12B):2555–2566. doi: 10.1101/gad.5.12b.2555. [DOI] [PubMed] [Google Scholar]
  27. Stern S., Tanaka M., Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. doi: 10.1038/341624a0. [DOI] [PubMed] [Google Scholar]
  28. Tanaka M., Grossniklaus U., Herr W., Hernandez N. Activation of the U2 snRNA promoter by the octamer motif defines a new class of RNA polymerase II enhancer elements. Genes Dev. 1988 Dec;2(12B):1764–1778. doi: 10.1101/gad.2.12b.1764. [DOI] [PubMed] [Google Scholar]
  29. Tanaka M., Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. doi: 10.1016/0092-8674(90)90589-7. [DOI] [PubMed] [Google Scholar]
  30. Tanaka M., Lai J. S., Herr W. Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. Cell. 1992 Feb 21;68(4):755–767. doi: 10.1016/0092-8674(92)90150-b. [DOI] [PubMed] [Google Scholar]
  31. Triezenberg S. J., Kingsbury R. C., McKnight S. L. Functional dissection of VP16, the trans-activator of herpes simplex virus immediate early gene expression. Genes Dev. 1988 Jun;2(6):718–729. doi: 10.1101/gad.2.6.718. [DOI] [PubMed] [Google Scholar]
  32. Vershon A. K., Johnson A. D. A short, disordered protein region mediates interactions between the homeodomain of the yeast alpha 2 protein and the MCM1 protein. Cell. 1993 Jan 15;72(1):105–112. doi: 10.1016/0092-8674(93)90054-t. [DOI] [PubMed] [Google Scholar]
  33. Walker S., Hayes S., O'Hare P. Site-specific conformational alteration of the Oct-1 POU domain-DNA complex as the basis for differential recognition by Vmw65 (VP16). Cell. 1994 Dec 2;79(5):841–852. doi: 10.1016/0092-8674(94)90073-6. [DOI] [PubMed] [Google Scholar]
  34. Wilson A. C., LaMarco K., Peterson M. G., Herr W. The VP16 accessory protein HCF is a family of polypeptides processed from a large precursor protein. Cell. 1993 Jul 16;74(1):115–125. doi: 10.1016/0092-8674(93)90299-6. [DOI] [PubMed] [Google Scholar]
  35. Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors. Methods Enzymol. 1983;100:468–500. doi: 10.1016/0076-6879(83)00074-9. [DOI] [PubMed] [Google Scholar]
  36. apRhys C. M., Ciufo D. M., O'Neill E. A., Kelly T. J., Hayward G. S. Overlapping octamer and TAATGARAT motifs in the VF65-response elements in herpes simplex virus immediate-early promoters represent independent binding sites for cellular nuclear factor III. J Virol. 1989 Jun;63(6):2798–2812. doi: 10.1128/jvi.63.6.2798-2812.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

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