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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kennedy, Mark W. Chalamalasetty, Ravindra B. Thomas, Sara Yamaguchi, Terry P. Garriock, Robert J. Jailwala, Parthav |
| Description | Author Affiliation: Kennedy MW ( Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD); Chalamalasetty RB ( Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD); Thomas S ( Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD); Garriock RJ ( Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD); Jailwala P ( Center for Cancer Research Collaborative Bioinformatics Resource, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.); Yamaguchi TP ( Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD); |
| Abstract | The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factors Sp5 and Sp8 (i.e., Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/ß-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/ß-catenin pathway. Sp5/8 bind directly to GC boxes in Wnt target gene enhancers and to adjacent, or distally positioned, chromatin-bound T-cell factor (Tcf) 1/lymphoid enhancer factor (Lef) 1 to facilitate recruitment of ß-catenin to target gene enhancers. Because Sp5 is itself directly activated by Wnt signals, we propose that Sp5 is a Wnt/ß-catenin pathway-specific transcript on factor that functions in a feed-forward loop to robustly activate select Wnt target genes. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 13 |
| Volume Number | 113 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2016-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA-Binding Proteins Metabolism Hepatocyte Nuclear Factor 1-alpha Lymphoid Enhancer-Binding Factor 1 Transcription Factors Wnt Signaling Pathway Genetics Beta Catenin Animals Embryonic Development Embryonic Stem Cells Cytology Enhancer Elements, Genetic Mice Mice, Transgenic Pregnancy Transcriptional Activation Research Support, N.I.H., Intramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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