启动子与基因座控制区转录结构域并列可激活基因表达。
The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression.
作者信息
Ho Yugong, Tadevosyan Aleksey, Liebhaber Stephen A, Cooke Nancy E
机构信息
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
出版信息
EMBO Rep. 2008 Sep;9(9):891-8. doi: 10.1038/embor.2008.126. Epub 2008 Jul 18.
Abstract
Nonlinear chromatin configurations can juxtapose widely separated elements within a genomic locus; however, it remains unclear how these structures are established and contribute to transcriptional control. A 5'-remote locus control region (LCR) regulates the human growth hormone (hGH-N) gene. HSI, a pituitary-specific component of the hGH LCR, establishes a domain of polymerase II (PolII) transcription 5' to hGH-N. Repression of this transcriptional domain by HSI deletion or PolII blockade decreases hGH-N expression. Here, we show that hGH-N activation is accompanied by positioning of the hGH-N promoter to this LCR transcriptional domain. Selectively blocking LCR transcription inhibits the formation of this active 'looped' conformation. Thus, HSI is crucial for establishing a domain of noncoding PolII transcription, and this domain is intimately linked with chromatin organization of the active hGH-N locus. This integration of LCR transcription with chromatin reconfiguration constitutes a robust pathway for long-range gene activation.
摘要
非线性染色质构型可使基因组位点内广泛分离的元件并列；然而，这些结构是如何建立的以及如何促进转录调控仍不清楚。一个5'远端基因座控制区（LCR）调控人类生长激素（hGH-N）基因。HSI是hGH LCR的垂体特异性组分，在hGH-N的5'端建立了一个聚合酶II（PolII）转录结构域。通过HSI缺失或PolII阻断对该转录结构域的抑制会降低hGH-N的表达。在这里，我们表明hGH-N的激活伴随着hGH-N启动子定位到该LCR转录结构域。选择性阻断LCR转录会抑制这种活跃的“环状”构象的形成。因此，HSI对于建立非编码PolII转录结构域至关重要，并且该结构域与活跃的hGH-N基因座的染色质组织密切相关。LCR转录与染色质重排的这种整合构成了一种强大的远程基因激活途径。
相似文献
1
The juxtaposition of a promoter with a locus control region transcriptional domain activates gene expression.启动子与基因座控制区转录结构域并列可激活基因表达。
EMBO Rep. 2008 Sep;9(9):891-8. doi: 10.1038/embor.2008.126. Epub 2008 Jul 18.
2
Locus control region transcription plays an active role in long-range gene activation.基因座控制区转录在远程基因激活中发挥着积极作用。
Mol Cell. 2006 Aug 4;23(3):365-75. doi: 10.1016/j.molcel.2006.05.041.
3
Distinct chromatin configurations regulate the initiation and the maintenance of hGH gene expression.不同的染色质构象调控 hGH 基因表达的起始和维持。
Mol Cell Biol. 2013 May;33(9):1723-34. doi: 10.1128/MCB.01166-12. Epub 2013 Feb 19.
4
A single base difference between Pit-1 binding sites at the hGH promoter and locus control region specifies distinct Pit-1 conformations and functions.人生长激素（hGH）启动子和基因座控制区的Pit-1结合位点之间的单个碱基差异决定了不同的Pit-1构象和功能。
Mol Cell Biol. 2006 Sep;26(17):6535-46. doi: 10.1128/MCB.00267-06.
5
DNase I hypersensitive site II of the human growth hormone locus control region mediates an essential and distinct long-range enhancer function.人类生长激素基因座控制区的 DNase I 超敏位点 II 介导必需且独特的长程增强子功能。
J Biol Chem. 2012 Jul 20;287(30):25454-65. doi: 10.1074/jbc.M112.365825. Epub 2012 Jun 5.
6
Autonomous actions of the human growth hormone long-range enhancer.人类生长激素远程增强子的自主作用。
Nucleic Acids Res. 2015 Feb 27;43(4):2091-101. doi: 10.1093/nar/gkv093. Epub 2015 Feb 6.
7
Expression of Pit-1 in nonsomatotrope cell lines induces human growth hormone locus control region histone modification and hGH-N transcription.Pit-1在非生长激素细胞系中的表达可诱导人生长激素基因座控制区组蛋白修饰和hGH-N转录。
J Mol Biol. 2009 Jul 3;390(1):26-44. doi: 10.1016/j.jmb.2009.04.081. Epub 2009 May 7.
8
A defined locus control region determinant links chromatin domain acetylation with long-range gene activation.一个明确的基因座控制区决定因素将染色质结构域乙酰化与远程基因激活联系起来。
Mol Cell. 2002 Feb;9(2):291-302. doi: 10.1016/s1097-2765(02)00447-1.
9
POU1F1-mediated activation of hGH-N by deoxyribonuclease I hypersensitive site II of the human growth hormone locus control region.POU1F1 介导的人生长激素基因调控区脱氧核糖核酸酶 I 超敏位点 II 对 hGH-N 的激活作用。
J Mol Biol. 2012 Jan 6;415(1):29-45. doi: 10.1016/j.jmb.2011.11.001. Epub 2011 Nov 9.
10
The human growth hormone locus control region mediates long-distance transcriptional activation independent of nuclear matrix attachment regions.人类生长激素基因座控制区介导独立于核基质附着区的远距离转录激活。
Nucleic Acids Res. 2001 Aug 15;29(16):3356-61. doi: 10.1093/nar/29.16.3356.
引用本文的文献
1
Evidence for Pituitary Repression of the Human Growth Hormone-Related Placental Lactogen Genes and a Role for P Sequences.垂体对人类生长激素相关胎盘催乳素基因的抑制作用及P序列的作用证据。
Int J Mol Sci. 2025 May 6;26(9):4421. doi: 10.3390/ijms26094421.
2
Sleep deprivation and diet affect human GH gene expression in transgenic mice in vivo.睡眠剥夺和饮食会影响转基因小鼠体内的人类生长激素（GH）基因表达。
Endocr Connect. 2020 Dec;9(12):1135-1147. doi: 10.1530/EC-20-0354.
3
Single-cell transcriptomic analysis of adult mouse pituitary reveals sexual dimorphism and physiologic demand-induced cellular plasticity.单细胞转录组分析揭示成年小鼠垂体的性别二态性和生理需求诱导的细胞可塑性。
Protein Cell. 2020 Aug;11(8):565-583. doi: 10.1007/s13238-020-00705-x. Epub 2020 Mar 19.
4
Evidence for a Circadian Effect on the Reduction of Human Growth Hormone Gene Expression in Response to Excess Caloric Intake.关于昼夜节律对因热量摄入过多而导致的人类生长激素基因表达降低的影响的证据。
J Biol Chem. 2016 Jun 24;291(26):13823-33. doi: 10.1074/jbc.M116.722744. Epub 2016 May 5.
5
Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster.基因座控制区的远程环化驱动多基因簇内的组织特异性染色质包装。
Nucleic Acids Res. 2016 Jun 2;44(10):4651-64. doi: 10.1093/nar/gkw090. Epub 2016 Feb 17.
6
Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD.与孤立性生长激素缺乏症相关的人类POU1F1突变的功能特征：一种导致孤立性生长激素缺乏症的新病因。
Hum Mol Genet. 2016 Feb 1;25(3):472-83. doi: 10.1093/hmg/ddv486. Epub 2015 Nov 26.
7
An autoregulatory pathway establishes the definitive chromatin conformation at the pit-1 locus.一条自调控通路在Pit-1基因座建立了确定的染色质构象。
Mol Cell Biol. 2015 May;35(9):1523-32. doi: 10.1128/MCB.01283-14. Epub 2015 Feb 17.
8
PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program.PRDM16 结合 MED1 并控制染色质结构以确定棕色脂肪转录程序。
Genes Dev. 2015 Feb 1;29(3):298-307. doi: 10.1101/gad.252734.114.
9
Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.能量稳态靶向人类生长激素1基因座的染色体重排。
J Clin Invest. 2014 Nov;124(11):5002-12. doi: 10.1172/JCI77126. Epub 2014 Oct 8.
10
Tissue specific CTCF occupancy and boundary function at the human growth hormone locus.组织特异性 CTCF 占据和人生长激素基因座的边界功能。
Nucleic Acids Res. 2014 Apr;42(8):4906-21. doi: 10.1093/nar/gku139. Epub 2014 Feb 21.
本文引用的文献
1
The complex language of chromatin regulation during transcription.转录过程中染色质调控的复杂语言。
Nature. 2007 May 24;447(7143):407-12. doi: 10.1038/nature05915.
2
Locus control region transcription plays an active role in long-range gene activation.基因座控制区转录在远程基因激活中发挥着积极作用。
Mol Cell. 2006 Aug 4;23(3):365-75. doi: 10.1016/j.molcel.2006.05.041.
3
The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation.在红细胞成熟过程中，小鼠β-珠蛋白基因座与活跃转录工厂的结合需要基因座控制区。
Genes Dev. 2006 Jun 1;20(11):1447-57. doi: 10.1101/gad.1419506. Epub 2006 May 16.
4
On a chromosome far, far away: LCRs and gene expression.在一条遥远的染色体上：LCRs与基因表达。
Trends Genet. 2006 Jan;22(1):38-45. doi: 10.1016/j.tig.2005.11.001. Epub 2005 Nov 23.
5
Long-range interactions between three transcriptional enhancers, active Vkappa gene promoters, and a 3' boundary sequence spanning 46 kilobases.三个转录增强子、活跃的Vκ基因启动子与一个跨越46千碱基的3'边界序列之间的长程相互作用。
Mol Cell Biol. 2005 Apr;25(8):3220-31. doi: 10.1128/MCB.25.8.3220-3231.2005.
6
Active genes dynamically colocalize to shared sites of ongoing transcription.活跃基因动态共定位于正在进行转录的共享位点。
Nat Genet. 2004 Oct;36(10):1065-71. doi: 10.1038/ng1423. Epub 2004 Sep 7.
7
Activation of the human GH gene cluster: roles for targeted chromatin modification.人类生长激素基因簇的激活：靶向染色质修饰的作用
Trends Endocrinol Metab. 2004 Jan-Feb;15(1):40-5. doi: 10.1016/j.tem.2003.11.004.
8
The beta-globin nuclear compartment in development and erythroid differentiation.发育和红细胞分化过程中的β-珠蛋白核区室
Nat Genet. 2003 Oct;35(2):190-4. doi: 10.1038/ng1244. Epub 2003 Sep 21.
9
Transcriptional elongation by RNA polymerase II and histone methylation.RNA聚合酶II介导的转录延伸与组蛋白甲基化
J Biol Chem. 2003 Jul 18;278(29):26303-6. doi: 10.1074/jbc.R300014200. Epub 2003 May 22.
10
The beta -globin locus control region (LCR) functions primarily by enhancing the transition from transcription initiation to elongation.β-珠蛋白基因座控制区（LCR）主要通过增强从转录起始到延伸的转变发挥作用。
Genes Dev. 2003 Apr 15;17(8):1009-18. doi: 10.1101/gad.1072303. Epub 2003 Apr 2.
Zotero 插件