胰腺同源盒基因STF-1中胰岛特异性增强子的激素调节。
Hormonal regulation of an islet-specific enhancer in the pancreatic homeobox gene STF-1.
作者信息
Sharma S, Jhala U S, Johnson T, Ferreri K, Leonard J, Montminy M
机构信息
Department of Biology, University of California, San Diego, La Jolla 92037, USA.
出版信息
Mol Cell Biol. 1997 May;17(5):2598-604. doi: 10.1128/MCB.17.5.2598.
Abstract
The homeobox protein STF-1 appears to function as a master control switch for expression of the pancreatic program during development. Here we characterize a composite enhancer which directs STF-1 expression to pancreatic islet cells via two functional elements that recognize the nuclear factors HNF-3beta and BETA-2. In keeping with their inhibitory effects on islet cell maturation, glucocorticoids were found to repress STF-1 gene expression by interfering with HNF-3beta activity on the islet-specific enhancer. Overexpression of HNF-3beta suppressed glucocorticoid receptor-mediated inhibition of the STF-1 gene, and our results suggest that the expansion of pancreatic islet precursor cells during development may be restricted by hormonal cues which regulate STF-1 gene expression.
摘要
同源框蛋白STF-1在发育过程中似乎起着胰腺程序表达主控制开关的作用。在此，我们鉴定了一个复合增强子，它通过识别核因子HNF-3β和BETA-2的两个功能元件将STF-1表达导向胰岛细胞。鉴于糖皮质激素对胰岛细胞成熟的抑制作用，发现其通过干扰HNF-3β在胰岛特异性增强子上的活性来抑制STF-1基因表达。HNF-3β的过表达抑制了糖皮质激素受体介导的STF-1基因抑制作用，我们的结果表明，发育过程中胰岛前体细胞的扩增可能受到调节STF-1基因表达的激素信号的限制。
相似文献
1
Hormonal regulation of an islet-specific enhancer in the pancreatic homeobox gene STF-1.胰腺同源盒基因STF-1中胰岛特异性增强子的激素调节。
Mol Cell Biol. 1997 May;17(5):2598-604. doi: 10.1128/MCB.17.5.2598.
2
A pancreatic beta -cell-specific enhancer in the human PDX-1 gene is regulated by hepatocyte nuclear factor 3beta (HNF-3beta ), HNF-1alpha, and SPs transcription factors.人类PDX-1基因中的胰腺β细胞特异性增强子受肝细胞核因子3β（HNF-3β）、HNF-1α和SPs转录因子调控。
J Biol Chem. 2001 May 18;276(20):17533-40. doi: 10.1074/jbc.M009088200. Epub 2001 Feb 5.
3
Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF.同源盒因子STF-1在胰岛中的表达依赖于一个与USF结合的E盒基序。
J Biol Chem. 1996 Jan 26;271(4):2294-9. doi: 10.1074/jbc.271.4.2294.
4
The homeodomain protein IPF-1/STF-1 is expressed in a subset of islet cells and promotes rat insulin 1 gene expression dependent on an intact E1 helix-loop-helix factor binding site.同源结构域蛋白IPF-1/STF-1在一部分胰岛细胞中表达，并依赖完整的E1螺旋-环-螺旋因子结合位点促进大鼠胰岛素1基因的表达。
Biochem J. 1995 Sep 15;310 ( Pt 3)(Pt 3):997-1003. doi: 10.1042/bj3100997.
5
Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1.胰岛细胞中的胰岛素表达依赖于螺旋-环-螺旋因子E47和同源盒因子STF-1之间的协同相互作用。
Mol Endocrinol. 1994 Dec;8(12):1798-806. doi: 10.1210/mend.8.12.7708065.
6
Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate beta-cell-specific expression.pdx-1基因中调控元件的功能保守性：PDX-1和肝细胞核因子3β转录因子介导β细胞特异性表达。
Mol Cell Biol. 2000 Oct;20(20):7583-90. doi: 10.1128/MCB.20.20.7583-7590.2000.
7
The cut-homeodomain transcriptional activator HNF-6 is coexpressed with its target gene HNF-3 beta in the developing murine liver and pancreas.切割同源结构域转录激活因子HNF-6与其靶基因HNF-3β在发育中的小鼠肝脏和胰腺中共同表达。
Dev Biol. 1997 Dec 15;192(2):228-46. doi: 10.1006/dbio.1997.8744.
8
Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver.生长激素调节牛肝脏中肝细胞核因子-3γ及其他肝脏富集转录因子的表达。
J Endocrinol. 2005 Jan;184(1):95-105. doi: 10.1677/joe.1.05821.
9
Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear factor 3 beta and Pax6.pdx-1基因组织特异性调控区域中的保守序列介导胰腺β细胞中的转录：肝细胞核因子3β和Pax6的作用。
Mol Cell Biol. 2002 Jul;22(13):4702-13. doi: 10.1128/MCB.22.13.4702-4713.2002.
10
Hes3 is expressed in the adult pancreatic islet and regulates gene expression, cell growth, and insulin release.Hes3在成年胰腺胰岛中表达，并调节基因表达、细胞生长和胰岛素释放。
J Biol Chem. 2014 Dec 19;289(51):35503-16. doi: 10.1074/jbc.M114.590687. Epub 2014 Nov 4.
引用本文的文献
1
Prevalence and Clinical Characteristics of NEUROD1-MODY in Chinese Early-Onset Type 2 Diabetes Mellitus and a Literature Review.中国早发2型糖尿病中NEUROD1-MODY的患病率及临床特征并文献综述
J Diabetes. 2025 Apr;17(4):e70080. doi: 10.1111/1753-0407.70080.
2
PDX1 is the cornerstone of pancreatic β-cell functions and identity.胰腺十二指肠同源盒蛋白1（PDX1）是胰腺β细胞功能和特性的基石。
Front Mol Biosci. 2022 Dec 15;9:1091757. doi: 10.3389/fmolb.2022.1091757. eCollection 2022.
3
Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning.确定Pdx1转录因子在断奶期间胰岛β细胞成熟和增殖中的新作用。
Diabetes. 2017 Nov;66(11):2830-2839. doi: 10.2337/db16-1516. Epub 2017 Jul 13.
4
Foxa2 and Pdx1 cooperatively regulate postnatal maturation of pancreatic β-cells.Foxa2 和 Pdx1 协同调节胰腺 β 细胞的出生后成熟。
Mol Metab. 2017 Mar 25;6(6):524-534. doi: 10.1016/j.molmet.2017.03.007. eCollection 2017 Jun.
5
Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4.基因靶向二肽基肽酶-4抑制剂在一名患有新型4型青少年发病的成年型糖尿病（MODY）突变患者中的应用
Clin Med Insights Endocrinol Diabetes. 2015 Oct 27;8:83-6. doi: 10.4137/CMED.S31926. eCollection 2015.
6
Regulation of Glucose Homeostasis by Glucocorticoids.糖皮质激素对葡萄糖稳态的调节
Adv Exp Med Biol. 2015;872:99-126. doi: 10.1007/978-1-4939-2895-8_5.
7
Genes involved in pancreatic islet cell rejuvenation.参与胰岛细胞再生的基因。
Indian J Med Res. 2013 Apr;137(4):695-703.
8
Fetal PGC-1α overexpression programs adult pancreatic β-cell dysfunction.过表达胎儿 PGC-1α 导致成年胰腺β细胞功能障碍。
Diabetes. 2013 Apr;62(4):1206-16. doi: 10.2337/db12-0314. Epub 2012 Dec 28.
9
Involvement of thioredoxin-interacting protein (TXNIP) in glucocorticoid-mediated beta cell death.硫氧还蛋白相互作用蛋白 (TXNIP) 在糖皮质激素介导的胰岛β细胞死亡中的作用。
Diabetologia. 2012 Apr;55(4):1048-57. doi: 10.1007/s00125-011-2422-z. Epub 2012 Jan 14.
10
Genomic sequencing of key genes in mouse pancreatic cancer cells.对小鼠胰腺癌细胞中关键基因进行基因组测序。
Curr Mol Med. 2012 Mar;12(3):331-41. doi: 10.2174/156652412799218868.
本文引用的文献
1
Role of CBP/P300 in nuclear receptor signalling.CBP/P300在核受体信号传导中的作用。
Nature. 1996 Sep 5;383(6595):99-103. doi: 10.1038/383099a0.
2
Hepatic specification of the gut endoderm in vitro: cell signaling and transcriptional control.体外肠道内胚层的肝脏特化：细胞信号传导与转录调控。
Genes Dev. 1996 Jul 1;10(13):1670-82. doi: 10.1101/gad.10.13.1670.
3
PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum.PDX-1是胰腺生长和十二指肠近端分化所必需的。
Development. 1996 Mar;122(3):983-95. doi: 10.1242/dev.122.3.983.
4
The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient mice.
Development. 1996 May;122(5):1409-16. doi: 10.1242/dev.122.5.1409.
5
Pancreatic islet expression of the homeobox factor STF-1 relies on an E-box motif that binds USF.同源盒因子STF-1在胰岛中的表达依赖于一个与USF结合的E盒基序。
J Biol Chem. 1996 Jan 26;271(4):2294-9. doi: 10.1074/jbc.271.4.2294.
6
Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5.肝细胞核因子3/叉头DNA识别基序的共晶体结构类似于组蛋白H5。
Nature. 1993 Jul 29;364(6436):412-20. doi: 10.1038/364412a0.
7
Hepatocyte nuclear factor 3/fork head or "winged helix" proteins: a family of transcription factors of diverse biologic function.肝细胞核因子3/叉头或“翼状螺旋”蛋白：一类具有多种生物学功能的转录因子家族。
Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10421-3. doi: 10.1073/pnas.90.22.10421.
8
Insulin-promoter-factor 1 is required for pancreas development in mice.胰岛素启动因子1是小鼠胰腺发育所必需的。
Nature. 1994 Oct 13;371(6498):606-9. doi: 10.1038/371606a0.
9
IDX-1: a new homeodomain transcription factor expressed in rat pancreatic islets and duodenum that transactivates the somatostatin gene.IDX-1：一种在大鼠胰岛和十二指肠中表达的新型同源结构域转录因子，可反式激活生长抑素基因。
EMBO J. 1994 Mar 1;13(5):1145-56. doi: 10.1002/j.1460-2075.1994.tb06363.x.
10
Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.
Development. 1995 Jan;121(1):11-8. doi: 10.1242/dev.121.1.11.
Zotero 插件