Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene

Jane B. Lian, Janet L. Stein, Gary S. Stein, Martin Montecino, André J. Van Wijnen, Amjad Javed, Soraya Gutierrez

Resultado de la investigación: Contribución a una revistaArtículo

33 Citas (Scopus)

Resumen

The vitamin D response element in the bone tissue-specific osteocalcin gene has served as a prototype for understanding molecular mechanisms regulating physiologic responsiveness of vitamin D-dependent genes in bone cells. We briefly review factors which contribute to vitamin D transcriptional control. The organization of the vitamin D response element (VDRE), the multiple activities of the vitamin D receptor transactivation complex, and the necessity for protein-protein interactions between the VDR-RXR heterodimer activation complex and DNA binding proteins at other regulatory elements, including AP-1 sites and TATA boxes, provide for precise regulation of gene activity in concert with basal levels of transcription. We present evidence for molecular mechanisms regulating vitamin D-dependent mediated transcription of the osteocalcin gene that involve chromatin structure of the gene and nuclear architecture. Modifications in nucleosomal organization, DNase I hypersensitivity and localization of vitamin D receptor interacting proteins in subnuclear domains are regulatory components of vitamin D-dependent gene transcription. A model is proposed to account for the inability of vitamin D induction of the osteocalcin gene in the absence of ongoing basal transcription by competition of the YY1 nuclear matrix-associated transcription factor for TFIIB-VDR interactions. Activation of the VDR-RXR complex at the OC VDRE occurs through modifications in chromatin mediated in part by interaction of OC gene regulatory sequences with the nuclear matrix-associated Cbfa1 (Runx2) transcription factor which is required for osteogenesis.

Idioma originalInglés
Páginas (desde-hasta)159-170
Número de páginas12
PublicaciónSteroids
Volumen66
N.º3-5
DOI
EstadoPublicada - 1 may 2001

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología molecular
  • Endocrinología
  • Farmacología
  • Bioquímica clínica
  • Química orgánica

Huella Profundice en los temas de investigación de 'Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene'. En conjunto forman una huella única.

  • Citar esto