Regulation of transcription-factor activity during growth and differentiation: involvement of the nuclear matrix in concentration and localization of promoter binding proteins
AuthorsStein, Gary S.
Lian, Jane B.
Dworetzky, Steven I.
Owen, T. A.
Bidwell, Joseph P.
Van Wijnen, Andre J.
UMass Chan AffiliationsDepartment of Medicine, Diabetes Division
Department of Cell Biology
Graduate School of Biomedical Sciences
KeywordsAnimals; Cell Differentiation; DNA Replication; DNA-Binding Proteins; Gene Expression Regulation; Nuclear Matrix; Promoter Regions (Genetics); Transcription Factors; Transcription, Genetic
Medicine and Health Sciences
MetadataShow full item record
AbstractSeveral 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.
SourceJ Cell Biochem. 1991 Dec;47(4):300-5. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32600
Related ResourcesLink to Article in PubMed