ENDOGENOUS RETROVIRAL SEQUENCES ARE REQUIRED FOR TISSUE-SPECIFIC EXPRESSION OF A HUMAN SALIVARY AMYLASE GENE

ENDOGENOUS RETROVIRAL SEQUENCES ARE REQUIRED FOR TISSUE-SPECIFIC EXPRESSION OF A HUMAN SALIVARY AMYLASE GENE
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DOI:
10.1101/gad.6.8.1457
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发表时间:
1992-08-01
影响因子:
10.5
通讯作者:
MEISLER, MH
MEISLER, MH
中科院分区:
生物学1区
文献类型:
--
作者:
TING, CN;ROSENBERG, MP;MEISLER, MH

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人唾液淀粉酶基因与两个插入元件相关,一个γ-肌动蛋白加工假基因和一个内源性逆转录病毒样元件。为了测试这些插入元件对组织特异性的贡献,建立了携带10种淀粉酶构建体的25系转基因小鼠。发现AMY 1C的1-kb片段(-1003至+2)足以用于人生长激素报告基因的腮腺特异性表达。1-kb片段完全来自插入序列。从-1003到-826的缺失导致转基因表达水平降低和组织特异性丧失。片段-1003至-327足以将腮腺特异性转移至胸苷激酶启动子。这些数据表明,人AMY 1C的功能性组织特异性启动子来自插入序列,腮腺表达可由仅来自逆转录病毒的序列赋予。这些和其他最近的观察表明,逆转录转座在基因调控的进化中的作用。
The human salivary amylase genes are associated with two inserted elements, a gamma-actin-processed pseudogene and an endogenous retroviral-like element. To test the contribution of these inserted elements to tissue specificity, 25 lines of transgenic mice carrying 10 amylase constructs were established. A 1-kb fragment of AMY1C (-1003 to +2) was found to be sufficient for parotid-specific expression of a human growth hormone reporter gene. The 1-kb fragment is entirely derived from inserted sequences. Deletion from -1003 to -826 resulted in reduced levels of transgene expression and loss of tissue specificity. The fragment -1003 to -327 was sufficient to transfer parotid specificity to the thymidine kinase promoter. The data demonstrate that the functional tissue-specific promoter of human AMY1C is derived from inserted sequences and that parotid expression can be conferred by sequences derived solely from the retrovirus. A role for retrotransposition in the evolution of gene regulation is indicated by these and other recent observations.