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Science 3 November 1995:
Vol. 270. no. 5237, pp. 815 - 819
DOI: 10.1126/science.270.5237.815

Reports

Participation of the Human -Globin Locus Control Region in Initiation of DNA Replication

Mirit I. Aladjem,  Mark Groudine,  Linnea L. Brody,  Ellen S. Dieken,  R. E. Keith Fournier,  Geoffrey M. Wahl (1),  Elliot M. Epner

The human beta-globin locus control region (LCR) controls the transcription, chromatin structure, and replication timing of the entire locus. DNA replication was found to initiate in a transcription-independent manner within a region located 50 kilobases downstream of the LCR in human, mouse, and chicken cells containing the entire human beta-globin locus. However, DNA replication did not initiate within a deletion mutant locus lacking the sequences that encompass the LCR. This mutant locus replicated in the 3` to 5` direction. Thus, interactions between distantly separated sequences can be required for replication initiation, and factors mediating this interaction appear to be conserved in evolution.


M. I. Aladjem, L. L. Brody, G. M. Wahl, Gene Expression Laboratory, Salk Institute, 10010 North Torrey Pines Road, San Diego, CA 92037, USA.
M. Groudine and E. M. Epner, Fred Hutchinson Cancer Research Center, Seattle, WA 98185, USA, and University of Washington, Seattle, WA 98195, USA.
E. S. Dieken and R. E. Keith Fournier, Fred Hutchinson Cancer Research Center, Seattle, WA 98185, USA.
(1) To whom correspondence should be addressed.


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