Genetic analysis of the human papillomavirus type 31 differentiation-dependent late promoter.
Human papillomaviruses infect stratifying squamous epithelia, causing benign and malignant lesions. Upon differentiation of the host keratinocyte, the virus undergoes a dramatic increase in both DNA replication and transcription from the late promoter, leading to expression of late genes and virion morphogenesis. In human papillomavirus type 31 (HPV31), the late promoter is designated p742 and includes multiple start sites embedded within the E7 gene. In this report, we mapped viral DNA elements that control transcriptional activity from p742. Enhancer elements in the viral upstream regulatory region positively regulate this promoter. The region containing the transcriptional start sites is dispensable for activity, and at least two separate elements in the E6/E7 region are capable of supporting transcription. Of these, we mapped one to a 150-bp region of the E7 open reading frame and designate it the core p742 promoter. Using GF109203X, an inhibitor of protein kinase C signaling, we show that p742 activation is independent of viral genome amplification. Finally, we mapped elements in the region of p742 that confer responsiveness to differentiation and show that the upstream regulatory region does not contribute to the differentiation response of p742. These studies are an important step toward understanding the functioning and regulation of this multiple-start promoter.
Bodily
Jason M
JM
Department of Microbiology and Immunology H107, P. O. Box 850, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Meyers
Craig
C
D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D015678:Viral Structural Proteins; D011493:Protein Kinase C; C070515:bisindolylmaleimide I
Proc Assoc Am Physicians. 1999 Nov-Dec;111(6):581-7
10591087
J Virol. 1992 Dec;66(12):7319-27
1331522
Nature. 1993 May 20;363(6426):281-3
8387645
J Biol Chem. 1994 Feb 18;269(7):5391-402
8106522
Virology. 1994 Nov 1;204(2):799-804
7941349
J Virol. 1995 Jun;69(6):3381-8
7745684
Virology. 1995 Aug 1;211(1):184-97
7645210
J Virol. 1995 Oct;69(10):6553-6
7666558
J Virol. 1996 Apr;70(4):2339-49
8642661
Trends Biochem Sci. 1996 Sep;21(9):327-35
8870495
Biochim Biophys Acta. 1996 Oct 9;1288(2):F55-78
8876633
Biochim Biophys Acta. 1997 Mar 20;1351(1-2):181-91
9116032
J Virol. 1997 Jul;71(7):5161-72
9188583
Genes Dev. 1997 Jul 15;11(14):1873-84
9242494
J Virol. 1997 Sep;71(9):6956-66
9261424
J Virol. 1997 Oct;71(10):7167-79
9311789
J Virol. 1997 Oct;71(10):7381-6
9311816
Virology. 1997 Oct 13;237(1):159-69
9344918
J Virol. 1998 Apr;72(4):2715-22
9525589
J Virol. 1998 Jun;72(6):5016-24
9573271
Virology. 1998 Sep 1;248(2):218-30
9721231
Virology. 1999 Jan 20;253(2):219-29
9918880
J Virol. 1999 Mar;73(3):1835-45
9971761
Virology. 1999 Apr 25;257(1):239-46
10208937
Cold Spring Harb Symp Quant Biol. 1998;63:21-31
10384267
J Virol. 1999 Sep;73(9):7185-92
10438805
J Virol. 2000 Jul;74(14):6622-31
10864676
Gene. 2001 Mar 7;265(1-2):11-23
11255003
J Virol. 2001 Oct;75(19):9302-11
11533193
J Virol. 2001 Oct;75(20):10005-13
11559836
Genes Dev. 2001 Oct 1;15(19):2503-8
11581155
J Virol. 2002 May;76(10):4723-33
11967289
J Virol. 2002 May;76(10):4798-809
11967297
Anal Biochem. 2002 Aug 15;307(2):341-7
12202253
J Virol. 2002 Oct;76(19):9702-15
12208949
J Invest Dermatol. 2002 Dec;119(6):1282-9
12485429
Exp Mol Med. 2002 Sep 30;34(4):259-64
12515390
Virology. 2003 Feb 15;306(2):197-202
12642092
Eur J Biochem. 2003 Apr;270(8):1791-801
12694192
Virology. 2003 Jul 20;312(1):1-7
12890615
J Virol. 2004 Jan;78(2):612-29
14694093
Virology. 2004 Apr 10;321(2):173-80
15051378
Vitam Horm. 2004;67:35-49
15110170
Nature. 1981 Mar 26;290(5804):304-10
6259538
J Mol Biol. 1981 Dec 15;153(3):589-618
6279878
Cell. 1984 Feb;36(2):381-9
6319019
J Virol. 1985 Dec;56(3):1002-13
2999418
EMBO J. 1985 Dec 1;4(12):3273-80
3912167
Virology. 1988 Apr;163(2):481-93
2833021
Mol Cell Biol. 1988 May;8(5):2021-33
2838741
J Biol Chem. 1988 Jul 25;263(21):10377-85
3392018
J Virol. 2000 Jun;74(11):5198-205
10799595
Anticancer Res. 1988 Sep-Oct;8(5A):851-9
3052257
J Virol. 1989 Jun;63(6):2567-77
2542572
Virology. 1989 Sep;172(1):331-40
2549716
Mol Cell Biol. 1990 Apr;10(4):1390-8
2320003
Cell Growth Differ. 1990 Dec;1(12):607-15
2288876
J Virol. 1991 May;65(5):2254-60
1850010
Oncogene. 1991 May;6(5):873-5
1646990
Virology. 1991 Sep;184(1):9-13
1651607
J Biol Chem. 1991 Aug 25;266(24):15771-81
1874734
Science. 1992 Aug 14;257(5072):971-3
1323879
J Virol. 1992 Oct;66(10):6070-80
1326657
Science. 1993 Apr 2;260(5104):78-82
7682011