Baf60c is a nuclear Notch signaling component required for the establishment of left-right asymmetry.
Notch-mediated induction of Nodal at the vertebrate node is a critical step in initiating left-right (LR) asymmetry. In mice and zebrafish we show that Baf60c, a subunit of the Swi/Snf-like BAF chromatin remodeling complex, is essential for establishment of LR asymmetry. Baf60c knockdown mouse embryos fail to activate Nodal at the node and also have abnormal node morphology with mixing of crown and pit cells. In cell culture, Baf60c is required for Notch-dependent transcriptional activation and functions to stabilize interactions between activated Notch and its DNA-binding partner, RBP-J. Brg1 is also required for these processes, suggesting that BAF complexes are key components of nuclear Notch signaling. We propose a critical role for Baf60c in Notch-dependent transcription and LR asymmetry.
Takeuchi
Jun K
JK
Department of Cardiovascular Research, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Lickert
Heiko
H
Bisgrove
Brent W
BW
Sun
Xin
X
Yamamoto
Masamichi
M
Chawengsaksophak
Kallayanee
K
Hamada
Hiroshi
H
Yost
H Joseph
HJ
Rossant
Janet
J
Bruneau
Benoit G
BG
D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D002467:Cell Nucleus / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055457:Nodal Protein; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D055457:Nodal Protein; C526008:Nodal protein, mouse; D051880:Receptors, Notch; C494055:Smarcd3 protein, mouse; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins