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Journal of Virology, August 2000, p. 7671-7677, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Characteristics of the Adeno-Associated Virus Preintegration Site in Human Chromosome 19: Open Chromatin Conformation and Transcription-Competent Environment

Stefania Lamartina, Elisabetta Sporeno, Elena Fattori, and Carlo Toniatti*

Department of Genetics, Istituto di Ricerche di Biologia Molecolare, I.R.B.M.-Piero Angeletti, 00040 Pomezia (Rome), Italy

Received 28 October 1999/Accepted 17 May 2000

Adeno-associated virus (AAV) establishes latency in infected cells by integrating into the cellular genome, with a high preference for a unique region, called AAVS1, of the human chromosome 19. The AAV proteins Rep78 and -68 are postulated to initiate the site-specific integration process by binding to a Rep binding site (RBS) in AAVS1. We provide further evidence to corroborate this model by demonstrating that the AAVS1 RBS in human cell lines is located near a DNase I hypersensitive "open" chromatin region and therefore is potentially easily accessible to Rep proteins. This open conformation is maintained in transgenic rats which carry an AAVS1 3.5-kb DNA fragment and are proficient for Rep-mediated site-specific integration. Interestingly, the core of the DNAse I hypersensitive site in AAVS1 corresponds to a sequence displaying transcriptional enhancer-like properties, suggesting that AAVS1 constitutes a transcription-competent environment. The implications of our findings for AAV physiology and gene therapy are discussed.

* Corresponding author. Mailing address: Istituto di Ricerche di Biologia Molecolare, I.R.B.M.-P. Angeletti, Via Pontina Km 30.600, 00040 Pomezia (Rome), Italy. Phone: 39-06-91093668. Fax: 39-06-91093654. E-mail: toniatti{at}irbm.it.

Journal of Virology, August 2000, p. 7671-7677, Vol. 74, No. 16
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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