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Nucleic Acids Research, 1989, Vol. 17, No. 21 8833-8852
© 1989

MOLECULAR BIOLOGY

A common protein binds to two silencers 5' to the human ß-globin gene

Patricia E. Berg*, Donna M. Williams+, Ruo-Lan Qian§, Roger B. Cohen1, Shi-Xian Cao{varphi}, Moshe Mittelman and Alan N. Schechter

Laboratory of Chemical Biology, National Institute of Diabetes, and Digestive and Kidney Diseases MD 20892, USA 1Laboratory of Molecular Hematology, National Institutes of Health Bethesda, MD 20892, USA

*To whom correspondence should be addressed at Bldg. 10, Room 9N-312, NIDDK, NIH, Bethesda, MD 20892, USA

Received April 18, 1989. Revised September 18, 1989. Accepted September 18, 1989.

The temporal sequence of expression of human globin genes during development suggests precise regulation of these genes. Recent studies have characterized a number of DNA sequences within or flanking the human p-globin gene which are important in its regulation and several proteins which bind to these sequences have been identified. We have found two proteins which bind 5' to the human beta-globin gene. One of these proteins, which we designate BP1, binds to two sequences, one between –550 and –527 bp relative to the cap site, the other between –302 and –294 bp. A second protein, BP2, binds to sequences between –275 and –263 bp. The binding sites for both BP1 and BP2 are in two regions which function as silencers in a transient expression assay using the human erythroleukemia cell line K562. These results and others presented here suggest that BP1 may act as a repressor protein. Negative regulation seems to be an important component of tissue and developmental specific globin gene regulation.

+Present address: Genetic Therapy, Inc., Gaithersburg, MD, USA

§Present address: Shanghai Institute of Cell Biology, Shanghai, China

{varphi}Present address: Toronto Western Hospital, Toronto, Canada


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