IgH Enhancer Function in an Ectothermic Vertebrate

变温脊椎动物中的 IgH 增强子功能

• 批准号: 6711709
• 负责人: GREGORY W WARR
• 金额: $ 23.85万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6711709
• 关键词: B lymphocyte; biochemical evolution; catfish; gene expression; genetic enhancer element; immunogenetics; immunoglobulin genes; mutant; site directed mutagenesis; surface plasmon resonance; transcription factor; transfection

APPLICANT'S DESCRIPTION: Although transcriptional enhancers are essential for the expression of the immunoglobulin heavy chain (IgH) locus, they are also needed for the additional functions of V(D)J joining, V-region hypermutation and immunoglobulin (Ig) class switch recombination. This research is directed towards understanding the function of the enhancer that drives expression of the IgH locus in the channel catfish, a teleost fish and therefore lacking Ig class switching. Preliminary results suggest that the catfish IgH enhancer functions through a novel interaction of transcription factors bound to multiple interacting octamer and muE5 sites. The role of these sites in the function of the enhancer will be dissected by site-directed mutagenesis, and the function of the mutated enhancer will be assessed in transient expression assays upon transfection into catfish B-cells. Catfish muE5-binding factor(s) will be isolated and characterized. The interactions between Oct transcription factors, muE5binding factors and the DNA motifs that they recognize will be measured directly using the BiaCore 2000 instrument that utilizes surface plasmon resonance detection. Such studies will define whether or not cooperative binding reactions occur between the Oct and muE5-binding transcription factors. Gene expression driven by the interaction of octamer-binding (Oct) transcription factors with those binding to muE5 sites (typically bHLH or zinc-finger transcription factors) has not been reported in mammalian systems. Thus, these studies should shed light on novel' transcription factor interactions in Ig enhancers, and will also provide insight into how enhancer function has influenced the evolution of the IgH locus.

申请人描述：虽然转录增强子是必不可少的

项目成果

Function of E-protein dimers expressed in catfish lymphocytes.

鲶鱼淋巴细胞中表达的E蛋白二聚体的功能。

• DOI: 10.1016/j.molimm.2007.08.001
• 发表时间: 2008
• 期刊: Molecular immunology
• 影响因子: 3.6
• 作者: Hikima,Jun-ichi;LennardRichard,MaraL;Wilson,MelanieR;Miller,NormanW;Warr,GregoryW
• 通讯作者: Warr,GregoryW

Oct2 transcription factors in fish--a comparative genomic analysis.

鱼类中的 Oct2 转录因子——比较基因组分析。

• DOI: 10.1016/j.fsi.2005.01.011
• 发表时间: 2006
• 期刊: Fish & shellfish immunology
• 影响因子: 4.7
• 作者: Lennard,MaraL;Wilson,MelanieR;Miller,NormanW;Clem,LWilliam;Warr,GregoryW;Hikima,Jun-ichi
• 通讯作者: Hikima,Jun-ichi

Characterization of an Oct1 orthologue in the channel catfish, Ictalurus punctatus: a negative regulator of immunoglobulin gene transcription?

斑点叉尾鮰中 Oct1 直系同源物的表征：免疫球蛋白基因转录的负调节因子？

• DOI: 10.1186/1471-2199-8-8
• 发表时间: 2007
• 期刊: BMC molecular biology
• 作者: Lennard,MaraL;Hikima,Jun-ichi;Ross,DavidA;Kruiswijk,CorineP;Wilson,MelanieR;Miller,NormanW;Warr,GregoryW
• 通讯作者: Warr,GregoryW

BOB.1 of the channel catfish, Ictalurus punctatus: not a transcriptional coactivator?

斑点叉尾鮰的 BOB.1：不是转录共激活因子？

• DOI: 10.1016/j.molimm.2008.10.005
• 发表时间: 2009
• 期刊: Molecular immunology
• 影响因子: 3.6
• 作者: Richard,MaraLLennard;Hikima,Jun-ichi;Wilson,MelanieR;Miller,NormanW;Cunningham,Charles;Warr,GregoryW
• 通讯作者: Warr,GregoryW