A MUSCLE-SPECIFIC ENHANCER IS LOCATED AT THE 3' END OF THE MYOSIN LIGHT-CHAIN 1/3 GENE LOCUS

A MUSCLE-SPECIFIC ENHANCER IS LOCATED AT THE 3' END OF THE MYOSIN LIGHT-CHAIN 1/3 GENE LOCUS
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DOI:
10.1101/gad.2.12b.1779
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发表时间:
1988-12-01
影响因子:
10.5
通讯作者:
ROSENTHAL, N
ROSENTHAL, N
中科院分区:
生物学1区
文献类型:
--
作者:
DONOGHUE, M;ERNST, H;ROSENTHAL, N

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两个骨骼肌球蛋白轻链MLC1和MLC3是由一个基因通过两个不同的启动子转录和前mRNAs的交替剪接而产生的。为了确定与MLC转录调控相关的DNA序列,我们构建了一系列将大鼠MLC基因片段与CAT基因连接的质粒载体,并检测了其在肌肉和非肌肉细胞中的表达。虽然两个MLC启动子附近的序列似乎不包含组织特异性调控元件,但位于MLC1启动子下游24kb的0.9kb DNA片段显著增加了分化的肌管中CAT基因的表达,但在未分化的成肌细胞或非肌肉细胞中不显著。这个片段以距离、启动子、位置和方向无关的方式激活基因表达到高水平的能力,将其定义为强大的肌肉特异性增强子元件。
Two skeletal myosin light chains, MLC1 and MLC3, are generated from a single gene by transcription from two different promoters and alternate splicing of the pre-mRNAs. To define DNA sequences involved in MLC transcriptional control, we constructed a series of plasmid vectors in which segments of the rat MLC locus were linked to a CAT gene and assayed for expression in muscle and nonmuscle cells. Whereas sequences proximal to the two MLC promoters do not appear to contain tissue-specific regulatory elements, a 0.9-kb DNA segment, located > 24 kb downstream of the MLC1 promoter, dramatically increases CAT gene expression in differentiated myotubes but not in undifferentiated myoblasts or nonmuscle cells. The ability of this segment to activate gene expression to high levels, in a distance-, promoter-, position-, and orientation-independent way, defines it as a strong muscle-specific enhancer element.