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

Our previous study showed that hydroxyurea (Hu) could induce HEL cells to express humanβ-globin gene. However the molecular mechanisms by which the expression of β-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 β-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 humanβ-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 β-globin gene and to promote its transcription.

Biological indicators of sub-optimal health status

OBJECTIVE:To investigate biological indicators of sub-optimal health status and provide means of objective assessment of sub-optimal health status.METHODS:We set the unified standards for diagnosing a SHS.We tested various laboratory indicators in 407 cases that we selected randomly from2807 subjects and collected 15 mL of fasting venous blood from each case.We measured serum immunoglobulin A(IgA)and immunoglobulin G(IgG)concentrations,serum beta endorphins(β-EP),cortisol(C),testosterone(T),plasma adrenocorticotropic hormone(ACTH)and serum T lymphocyte subsets CD3+and CD4+.RESULTS:Mean serum testosterone concentrations and their ratio to cortisol(C)concentrations weresignificantly higher in the healthy group than in those with sub-optimal health status(P<0.01).Mean serum CD3+concentrations were significantly higher in those with sub-optimal health status than in the healthy group(P<0.05).CONCLUSION:Decreased serum testosterone/cortisol ratio may be an objective indication of sub-optimal health status.Changes in neuroendocrine and immunological indicators may explain some of the symptoms,including malaise and poor work performance,attributable to persistent or relapsing fatigue in subjects with sub-optimal health status.