SALL4 is directly activated by TCF/LEF in the canonical Wnt signaling pathway.
The SALL4 promoter has not yet been characterized. Animal studies showed that SALL4 is downstream of and interacts with TBX5 during limb and heart development, but a direct regulation of SALL4 by TBX5 has not been demonstrated. For other SAL genes, regulation within the Shh, Wnt, and Fgf pathways has been reported. Chicken csal1 expression can be activated by a combination of Fgf4 and Wnt3a or Wnt7a. Murine Sall1 enhances, but Xenopus Xsal2 represses, the canonical Wnt signaling. Here we describe the cloning and functional analysis of the SALL4 promoter. Within a minimal promoter region of 31bp, we identified a consensus TCF/LEF-binding site. The SALL4 promoter was strongly activated not only by LEF1 but also by TCF4E. Mutation of the TCF/LEF-binding site resulted in decreased promoter activation. Our results demonstrate for the first time the direct regulation of a SALL gene by the canonical Wnt signaling pathway.
Böhm
Johann
J
Institut für Humangenetik und Anthropologie, Universität Freiburg, Freiburg, Germany.
Sustmann
Claudio
C
Wilhelm
Christian
C
Kohlhase
Jürgen
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000502:physiology*
C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; C472575:SALL4 protein, human; D051820:TCF Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins