SHORT COMMUNICATION

Cell Research (2002); 12(5-6):411-416

The interaction between the human b-globin locus control region and nuclear matrix

Shu Bing ZHANG, Ruo Lan QIAN^*

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China

Received Jun-13-2002   Revised Oct-31-2002   Accepted Nov-2-2002

Correspondence: Prof. Ruo Lan QIAN Tel: 0086-21-64315030-2092  Fax: 0086-21-64331090 E-mail: qianlab@sunm.shcnc.ac.cn

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Abstract

Our previous study showed that hydroxyurea (Hu) could induce HEL cells to express human b-globin gene. However the molecular mechanisms by which the expression of b-globin gene is activated and regulated are poorly understood. Here we show that the binding patterns between the core DNA sequences (HS2 core sequence -10681 ~ -10971 bp , HS3 core sequence -14991 ~ -14716 bp and HS4 core sequence -18586 ~ -18306 bp) of DNase I hypersensitive sites in the human b-globin LCR and nuclear matrix proteins isolated from Hu induced and uninduced HEL cells are quite different. Results demonstrated that nuclear matrix proteins might play important roles in regulating the expression of human b-like globin genes through their interaction with HSs (HS2,HS3 and HS4 core sequences) in the LCR. Moreover, the results obtained from the in vitro DNA-matrix binding assay showed that the core DNA sequences of DNase I hypersensitive sites (HS2, HS3 and HS4) were unable to bind to the nuclear matrix isolated from uninduced HEL cells; in addition, HS2 core DNA sequence was capable of binding to the nuclear matrix prepared from Hu-induced HEL cells, while both HS3 and HS4 core DNA sequences could not do so. Results indicated that the HS2 core DNA sequence may be a functional MAR (matrix attachment region). We suggest that the HS2 core DNA sequence binding to the nuclear matrix in Hu-induced HEL cells may open the structure of chromatin to make the LCR accessible to the promoter of b-globin gene and to promote its transcription.

Key words: human b-globin LCR, nuclear matrix proteins, nuclear matrix, HEL cells.