Regulation of transcription-factor activity during growth and differentiation: involvement of the nuclear matrix in concentration and localization of promoter binding proteins
Graduate School of Biomedical Sciences; Department of Cell Biology; Department of Medicine, Diabetes Division
Life Sciences | Medicine and Health Sciences
Several lines of evidence are presented which support involvement of the nuclear matrix in regulating the transcription of two genes, histone and osteocalcin, that are reciprocally expressed during development of the osteoblast phenotype. In the 5' regulatory region of an H4 histone gene, which is expressed in proliferating osteoblasts early during the developmental/differentiation sequence, a dual role is proposed for the nuclear matrix binding domain designated NMP-1 (-589 to -730 upstream from the transcription start site). In addition to functioning as a nuclear matrix attachment site, the sequences contribute to the upregulation of histone gene transcription, potentially facilitated by concentration and localization of an 84kD ATF DNA binding protein. A homologous nuclear matrix binding domain was identified in the promoter of the osteocalcin gene, which is expressed in mature osteoblasts in an extracellular matrix undergoing mineralization. The NMP binding domain in the osteocalcin gene promoter resides contiguous to the vitamin D responsive element. Together with gene and transcription factor localization, a model is proposed whereby nuclear matrix-associated structural constraints on conformation of the osteocalcin gene promoter facilitates vitamin D responsiveness mediated by cooperativity at multiple regulatory elements.
DOI of Published Version
J Cell Biochem. 1991 Dec;47(4):300-5. Link to article on publisher's site
Journal of cellular biochemistry
Stein, Gary S.; Lian, Jane B.; Dworetzky, Steven I.; Owen, T. A.; Bortell, Rita; Bidwell, Joseph P.; and Van Wijnen, Andre J., "Regulation of transcription-factor activity during growth and differentiation: involvement of the nuclear matrix in concentration and localization of promoter binding proteins" (1991). GSBS Student Publications. 1163.