SEQUENCES IN THE HUMAN PARATHYROID-HORMONE GENE THAT BIND THE 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR AND MEDIATE TRANSCRIPTIONAL REPRESSION IN RESPONSE TO 1,25-DIHYDROXYVITAMIN-D3

被引:303
作者
DEMAY, MB [1 ]
KIERNAN, MS [1 ]
DELUCA, HF [1 ]
KRONENBERG, HM [1 ]
机构
[1] UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BIOCHEM,MADISON,WI 53706
关键词
D O I
10.1073/pnas.89.17.8097
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
1,25-dihydroxyvitamin D3 [1,25(OH)2D3], plays an important role in the regulation of mineral ion homeostasis. As well as being the major steroid hormone that regulates calcium metabolism, 1,25(OH)2D3 suppresses transcription of the gene encoding parathyroid hormone, a peptide that plays a dominant role in regulating extracellular calcium levels. To identify DNA sequences that may mediate this transcriptional repression, nuclear extracts containing the 1,25(OH)2D3 receptor were examined for binding to sequences in the 5'-flanking region of the human parathyroid hormone gene. A 25-base-pair (bp) oligonucleotide containing the sequences from -125 to -101 from the start of exon I binds nuclear proteins recognized by monoclonal antibodies against the 1,25(OH)2D3 receptor. The sequences in this region contain a single copy of a motif (AGGTTCA) homologous to the motifs repeated in the up-regulatory 1,25(OH)2D3-response elements. When placed upstream to a heterologous viral promoter, the sequences contained in this 25-bp oligonucleotide mediate transcriptional repression in response to 1,25(OH)2D3 in GH4C1 cells but not in ROS 17/2.8 cells. This down-regulatory element, therefore, differs from the up-regulatory 1,25(OH)2D3-response elements both in sequence composition and in the requirement for particular cellular factors other than the 1,25(OH)2D3 receptor for repressing transcription.
引用
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页码:8097 / 8101
页数:5
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