Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2.
The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGF beta and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGF beta and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGF beta-related factor, which is most likely Nodal itself.
Saijoh
Y
Y
Division of Molecular Biology, Osaka University, Japan.
Adachi
H
H
Sakuma
R
R
Yeo
C Y
CY
Yashiro
K
K
Watanabe
M
M
Hashiguchi
H
H
Mochida
K
K
Ohishi
S
S
Kawabata
M
M
Miyazono
K
K
Whitman
M
M
Hamada
H
H
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D005246:Feedback; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D055458:Left-Right Determination Factors; D051379:Mice; D008822:Mice, Transgenic; D055457:Nodal Protein; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014982:Xenopus laevis
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D055458:Left-Right Determination Factors; D055457:Nodal Protein; C526008:Nodal protein, mouse; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta