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CD11b基因的启动子指导髓系特异性和发育调控的表达。

The promoter of the CD11b gene directs myeloid-specific and developmentally regulated expression.

作者信息

Shelley C S, Arnaout M A

机构信息

Leukocyte Biology and Inflammation Program, Harvard Medical School, Charlestown, MA.

出版信息

Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10525-9. doi: 10.1073/pnas.88.23.10525.

Abstract

Human CD11b/CD18 (complement receptor type 3) is a member of the beta 2 integrin subfamily which also includes the heterodimers CD11a/CD18 and CD11c/CD18. The CD11 molecules and the common CD18 are the products of different genes that exhibit distinct though overlapping patterns of tissue- and developmental-specific expression. Whereas expression of CD11b and CD11c is almost exclusively restricted to cells of the myeloid lineage, that of CD11a and CD18 is panleukocytic. To begin to understand the mechanisms by which expression of these gene products is restricted to leukocytes and leukocyte subpopulations and to elucidate the mechanisms by which their expression is coordinated, we have cloned and characterized the promoter region of the CD11b gene. A single transcription initiation site has been identified and the region extending 242 base pairs upstream and 71 base pairs downstream of this site has been shown to be sufficient to direct tissue-, cell-, and development-specific expression in vitro, which mimics that of the CD11b gene in vivo. Within this region there are potential binding sites for transcription factors known to be involved in hematopoietic-specific and phorbol ester-inducible gene expression. Further analysis of this region of the CD11b gene and comparison with the promoters of the CD11a, CD11c, and CD18 genes should lead to significant insights into the molecular mechanisms by which these genes are regulated during hematopoietic development and upon activation.

摘要

人CD11b/CD18(补体受体3型)是β2整合素亚家族的成员,该亚家族还包括异二聚体CD11a/CD18和CD11c/CD18。CD11分子和共同的CD18是不同基因的产物,它们在组织和发育特异性表达模式上表现出不同但重叠的情况。虽然CD11b和CD11c的表达几乎完全局限于髓系谱系的细胞,但CD11a和CD18的表达则是全白细胞性的。为了开始理解这些基因产物的表达是如何局限于白细胞和白细胞亚群的机制,并阐明它们的表达是如何协调的机制,我们克隆并鉴定了CD11b基因的启动子区域。已确定了一个单一的转录起始位点,并且已证明该位点上游延伸242个碱基对和下游延伸71个碱基对的区域足以在体外指导组织、细胞和发育特异性表达,这与CD11b基因在体内的表达情况相似。在该区域内,存在已知参与造血特异性和佛波酯诱导基因表达的转录因子的潜在结合位点。对CD11b基因的这一区域进行进一步分析,并与CD11a、CD11c和CD18基因的启动子进行比较,应该会对这些基因在造血发育和激活过程中受到调控的分子机制有重要的深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbb2/52961/5335cbc4fc27/pnas01073-0163-a.jpg

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