Dataset Information

Hairy and Enhancer of Split-Related With YRPW Motif-Like (HeyL) Is Dispensable for Bone Remodeling in Mice.

ABSTRACT: Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2, and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex-matched littermate controls was performed. µCT demonstrated modest cancellous bone osteopenia in 1 month old male mice and normal microarchitecture in 3 month old male HeyL null mice. Female HeyL null mice were not different from controls at either 1 or 3 months of age. Bone histomorphometry did not demonstrate differences between HeyL null mice of either sex and littermate controls. In conclusion, HeyL null mice do not exhibit an obvious skeletal phenotype demonstrating that HeyL is dispensable for skeletal homeostasis. J. Cell. Biochem. 118: 1819-1826, 2017. © 2016 Wiley Periodicals, Inc.

SUBMITTER: Canalis E

PROVIDER: S-EPMC5424199 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Hairy and Enhancer of Split-Related With YRPW Motif-Like (HeyL) Is Dispensable for Bone Remodeling in Mice.

Canalis Ernesto E Zanotti Stefano S

Journal of cellular biochemistry 20170309 7

Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2, and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) ...[more]

PMID: 28019674

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Project description:Peroxisome proliferator-activated receptor gamma (PPAR?) is a master regulator for white adipocyte differentiation and lipid storage. The increased level of hepatic PPAR?2 isoform reprograms liver for lipid storage and causes abnormal fat accumulation in certain pathophysiologic conditions. The current study aimed to investigate a role of transcriptional repressor hairy and enhancer of split 6 (HES6) in the regulation of Pparg2 expression and hepatic steatosis induced by diet. Liver-specific overexpression of Hes6 using adenovirus reduced Pparg2 messenger RNA levels by 90% and hepatic triglyceride accumulation by 22% compared to the levels in mice injected with an adenoviral empty vector with Western diet feeding. In sharp contrast, silencing Hes6 gene expression using short hairpin RNA increased hepatic lipid accumulation and Pparg2 messenger RNA levels by 70% and 4-fold, respectively. To locate hepatocyte nuclear factor 4 alpha (HNF4?) binding site(s), through which repressional activity of HES6 is mediated, a 2.5-kb Pparg2 promoter-driven luciferase reporter was constructed for transient transfection assays. Subsequently, chromatin immunoprecipitation and electrophoretic mobility shift assays were performed. An HNF4? binding consensus sequence was identified at 903 base pairs upstream from the transcription start site of Pparg2. Deletion or point mutation of the sequence in a luciferase reporter containing the Pparg2 promoter abolished HNF4?-mediated activation in HeLa cells. Chromatin immunoprecipitation and electrophoretic mobility shift assays further confirmed direct recruitment and binding of HNF4? to the site. Gene expression analysis with liver samples from subjects with nonalcoholic steatohepatitis suggested that the axis of the Hes6-Hnf4a-Pparg2 transcriptional cascade is also responsible for hepatic fat accumulation in humans. Conclusion: HES6 represses Pparg2 gene expression, thereby preventing hepatic lipid accumulation induced by chronic Western diet feeding or pathophysiologic conditions. (Hepatology Communications 2017;1:1085-1098).

Dataset Information

Hairy and Enhancer of Split-Related With YRPW Motif-Like (HeyL) Is Dispensable for Bone Remodeling in Mice.

Publications

Hairy and Enhancer of Split-Related With YRPW Motif-Like (HeyL) Is Dispensable for Bone Remodeling in Mice.

Similar Datasets

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