Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2.
Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation. With the use of transgenic analysis, the transcriptional regulatory regions of these genes responsible for their L-R asymmetric expression have now been investigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream region of lefty-2 reproduced the expression pattern of the corresponding gene. Examination of deletion constructs revealed the presence of a left side-specific enhancer (ASE) that is essential and sufficient for lefty-2 asymmetric expression. In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS). The 9. 5-kb region of lefty-1 and the 5.5-kb region of lefty-2 responded to iv and inv, upstream genes of lefty-1 and lefty-2. The regulation of lefty-2 by iv and inv was mediated by ASE. These results suggest that, in spite of the similarities between lefty-1 and lefty-2, different regulatory mechanisms underlie their asymmetric expression.
Saijoh
Y
Y
Division of Molecular Biology, Institute for Molecular and Cellular Biology, Osaka University, Suita, Osaka 565, Japan.
Adachi
H
H
Mochida
K
K
Ohishi
S
S
Hirao
A
A
Hamada
H
H
D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D055458:Left-Right Determination Factors; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*