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Molecular and Cellular Biology, January 1999, p. 671-679, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Analysis of Mice with Single and Multiple Copies of Transgenes Reveals a Novel Arrangement for the lambda 5-VpreB1 Locus Control Region

Pierangela Sabbattini, Andrew Georgiou, Calum Sinclair, and Niall Dillon*

Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom

Received 16 July 1998/Returned for modification 7 September 1998/Accepted 19 October 1998

The murine lambda 5-VpreB1 locus encodes two proteins that form part of the pre-B-cell receptor and play a key role in B-lymphocyte development. We have identified a locus control region (LCR) which is responsible for coordinate activation of both genes in pre-B cells. Analysis of mice with single and multiple copies of transgenes shows a clear difference in the expression behavior of the genes depending on the transgene copy number. While expression of both lambda 5 and VpreB1 in single- and two-copy integrations requires the presence of a set of DNase I hypersensitive sites located 3' of the lambda 5 gene, small fragments containing the genes have LCR activity when arranged in multiple-copy tandem arrays, indicating that additional components of the LCR are located within or close to the genes. The complete LCR is capable of driving efficient copy-dependent expression of a lambda 5 gene in pre-B cells even when it is integrated into centomeric gamma -satellite DNA. The finding that activation of expression of the locus by positively acting factors is fully dominant over the silencing effect of heterochromatin has implications for models for chromatin-mediated gene silencing during B-cell development.

* Corresponding author. Mailing address: Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd., London W12 0NN, United Kingdom. Phone: 44 181 383 8233. Fax: 44 181 383 8338. E-mail: ndillon{at}rpms.ac.uk.

Molecular and Cellular Biology, January 1999, p. 671-679, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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