TY - JOUR
T1 - Regulation of transcription‐factor activity during growth and differentiation
T2 - Involvement of the nuclear matrix in concentration and localization of promoter binding proteins
AU - Stein, Gary S.
AU - Lian, Jane B.
AU - Dworetzky, Steven I.
AU - Owen, Thomas A.
AU - Bortell, Rita
AU - Bidwell, Joseph P.
AU - van Wijnen, Andre J.
PY - 1991/12
Y1 - 1991/12
N2 - 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.
AB - 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.
KW - CCAAT box
KW - histone promoter
KW - hormone control
KW - osteocalcin promoter
KW - regulatory elements
KW - transcription factors
KW - vitamin D gene regulation
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U2 - 10.1002/jcb.240470403
DO - 10.1002/jcb.240470403
M3 - Article
C2 - 1795014
AN - SCOPUS:0026343139
SN - 0730-2312
VL - 47
SP - 300
EP - 305
JO - Journal of cellular biochemistry
JF - Journal of cellular biochemistry
IS - 4
ER -