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RISS 인기검색어
- 검색키워드
- 저자 : ( Yunwon Moon ) (검색결과 4 건)
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Distinct hypoxic regulation of preadipocyte factor-1 (Pref-1) in preadipocytes and mature adipocytes
Moon, Yunwon,Lee, Seongyeol,Park, Bongju,Park, Hyunsung Elsevier 2018 Biochimica et biophysica acta, Molecular cell rese Vol.1865 No.2
<P><B>Abstract</B></P> <P>Preadipocyte factor-1 (Pref-1) is a secretory soluble protein, which exerts pleiotropic effects on maintenance of cancer stem cell characteristics and commitment of mesenchymal stem cell lineages by inhibiting adipogenesis. Observations that obesity renders the microenvironment of adipose tissues hypoxic and that hypoxia inhibits adipogenesis lead us to investigate whether hypoxia increases the expression of anti-adipogenic Pref-1 in preadipocytes, mature adipocytes, and adipose tissues from obese mouse. In 3T3-L1 preadipocytes, hypoxia induces <I>Pref-1</I> by a hypoxia-inducible factor 1 (HIF-1)-dependent mechanism accompanied by increase in the levels of the active histone mark, acetylated H3K9/14 (H3K9/14Ac). Adipogenesis increased the levels of the heterochromatin histone mark, trimethylated H3K27 (H3K27me3), whereas it decreased the levels of H3K4me3 and H3K9/14Ac euchromatin marks of the mouse <I>Pref-1</I> promoter. However, differently from preadipocytes, in mature adipocytes hypoxia failed to reverse the repressive epigenetic changes of <I>Pref-1</I> promoter and to increase its expression. Short term (8weeks) high fat diet (HFD) increased HIF-1α protein in subcutaneous and epididymal adipose tissues, but did not increase <I>Pref-1</I> expression. Unlike in 3T3-L1 preadipocytes, HIF-1α did not increase <I>Pref-1</I> expression in adipose tissues in which mature adipocytes constitute the main population. Interestingly, long term (35weeks) HFD increased Pref-1 in serum but not in obese adipose tissues. This study suggests that Pref-1 is an endocrine factor which is synergistically increased by obesity and age.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prolonged-HFD increased the serum levels of Pref-1. </LI> <LI> Hypoxia induces Pref-1 in preadipocytes but not in adipocytes. </LI> <LI> Adipogenesis increased the repressive histone mark, H3K27me3 of Pref-1 promoter. </LI> </UL> </P>
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BMB Reports : Hypoxic repression of CYP7A1 through a HIF-1α-and SHP-independent mechanism
( Yunwon Moon ),( Bongju Park ),( Hyunsung Park ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.3
Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor- 1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1. [BMB Reports 2016; 49(3): 173-178]
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Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia
Lee, Seongyeol,Lee, Jieon,Chae, Sehyun,Moon, Yunwon,Lee, Ho-Youl,Park, Bongju,Yang, Eun Gyeong,Hwang, Daehee,Park, Hyunsung Oxford University Press 2017 Nucleic acids research Vol.45 No.20
<P><B>Abstract</B></P><P>Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia.</P>
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Hypoxia-inducible Factor-2α-dependent Hypoxic Induction of Wnt10b Expression in Adipogenic Cells
Park, Young-Kwon,Park, Bongju,Lee, Seongyeol,Choi, Kang,Moon, Yunwon,Park, Hyunsung American Society for Biochemistry and Molecular Bi 2013 The Journal of biological chemistry Vol.288 No.36
<P>Adipocyte hyperplasia and hypertrophy in obesity can lead to many changes in adipose tissue, such as hypoxia, metabolic dysregulation, and enhanced secretion of cytokines. In this study, hypoxia increased the expression of Wnt10b in both human and mouse adipogenic cells, but not in hypoxia-inducible factor (HIF)-2α-deficient adipogenic cells. Chromatin immunoprecipitation analysis revealed that HIF-2α, but not HIF-1α, bound to the <I>Wnt10b</I> enhancer region as well as upstream of the <I>Wnt1</I> gene, which is encoded by an antisense strand of the <I>Wnt10b</I> gene. Hypoxia-conditioned medium (H-CM) induced phosphorylation of lipoprotein-receptor-related protein 6 as well as β-catenin-dependent gene expression in normoxic cells, which suggests that H-CM contains canonical Wnt signals. Furthermore, adipogenesis of both human mesenchymal stem cells and mouse preadipocytes was inhibited by H-CM even under normoxic conditions. These results suggest that O<SUB>2</SUB> concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation.</P>
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