RESEARCH ARTICLE


NFI is an Essential Positive Transcription Factor for Human Papillomavirus Type 16 Early Gene Expression



Amy Baldwin1, Melissa K Hypes2, Lucia Pirisi3, Kim E Creek*, 3
1 The Channing Laboratory, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
2 Virginia Department of Forensic Science, Roanoke, VA 24019, USA
3 Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, and South Carolina Cancer Center, Columbia, SC 29203, USA

Article Information


Identifiers and Pagination:

Year: 2007
Volume: 1
First Page: 33
Last Page: 38
Publisher Id: TOVJ-1-33
DOI: 10.2174/1874357900701010033

Article History:

Received Date: 12/10/2007
Revision Received Date: 6/11/2007
Acceptance Date: 12/11/2007
Electronic publication date: 22/11/2007
Collection year: 2007

2007 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Department of Pathology Microbiology & Immunnology, University of South Carolina School of Medicine, South Carolina Cancer Center, 14 Richland Medical Park, Suite 500, Columbia, SC 29203, USA; Tel: (803) 434-3581; Fax: (803) 434-6388; E-mail: creek@med.sc.edu


Abstract

Human papillomavirus type 16 (HPV16) is the primary etiologic agent for greater than 50% of all cervical carcinomas. Expression of the HPV16 E6 and E7 oncoproteins is under control of the upstream regulatory region (URR), which contains a myriad of transcription factor binding sites, including 7 half sites for NFI. These NFI binding sites were used as probes in electrophoretic mobility shift assays (EMSAs), and mutational analysis of individual and multiple NFI binding sites was performed in order to demonstrate the relative importance of particular NFI sites to URR activity. By using 5 NFI half sites as an enhancer, we were able to detect a 4-fold increase in URR activity. Our results define the role and relative contribution of NFI binding sites to the basal activity of the HPV16 promoter, and demonstrate that NFI binding sites can act independently to enhance HPV16 URR activity in immortalized keratinocytes.