Regulation of RANKL promoter activity is associated with histone remodeling in murine bone stromal cells

Journal of Cellular Biochemistry
Xian FanJanet Rubin

Abstract

Receptor activator of NFkappa-B ligand (RANKL) is essential for osteoclast formation, function, and survival. Although RANKL mRNA and protein levels are modulated by 1,25(OH)2D3 and other osteoactive factors, regulatory mechanisms remain unclear. In this study, we show that 2 kb or 2 kb plus exon 1 of a RANKL promoter sequence conferred neither 1,25(OH)2D3 response nor tissue specificity. The histone deacetylase inhibitors trichostatin A (TSA) and sodium butyrate (SB), however, strongly increased RANKL promoter activity. A series of 5'-deleted RANKL promoter constructs from 2,020 to 110 bp showed fourfold increased activity after TSA treatment. TSA also dose dependently enhanced endogenous RANKL mRNA expression with 50 microM of TSA treatment causing equivalent RANKL expression to that seen with 1 nM 1,25(OH)2D3. Using a chromatin immunoprecipitation (ChIP) assay we showed that TSA significantly enhanced association of both acetylated histone H3 and H4 on the RANKL promoter, with H4 > H3. A similar increase in acetylated histone H4 on the RANKL gene locus was seen after 1,25(OH)2D3 treatment, but ChIP assay did not reveal localization of VDR/RXR heterodimers on the putative VDRE of the RANKL promoter. To explore the role of H4 ...Continue Reading

References

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Citations

Aug 27, 2011·Reviews in Endocrine & Metabolic Disorders·J Wesley PikeKathleen A Bishop
Oct 21, 2009·The Journal of Biological Chemistry·Buer SenJanet Rubin
Sep 1, 2009·Bone·Charles A O'Brien
Aug 17, 2016·International Journal of Molecular Sciences·Francesca MariniMaria Luisa Brandi
Sep 7, 2016·International Journal of Molecular Sciences·Chafik Ghayor, Franz E Weber
Jul 31, 2007·Journal of Cellular Biochemistry·Jennifer J Westendorf
Dec 21, 2005·Journal of Cellular Biochemistry·Hiroshi KajiyaSakamuri V Reddy
Dec 20, 2013·Clinical Chemistry and Laboratory Medicine : CCLM·Peter VrtačnikBarbara Ostanek
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cinzia FiondaMarco Cippitelli
Jun 16, 2019·International Journal of Oral Science·Liam Lawlor, Xuebin B Yang
Feb 12, 2021·Frontiers in Cell and Developmental Biology·Fei XuGuobin Liu

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