Klaus H. Kaestner

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Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Krüppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4(More)
The winged helix/forkhead class of transcription factors is characterized by a 100-amino-acid, monomeric DNAbinding domain. The structure of the DNA-binding domain of one of the class members, hepatocyte nuclear factor 3 g (HNF3g), in a complex with a DNA target has been solved (Clark et al. 1993). The DNA-binding domain folds into a variant of the(More)
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein(More)
Transcriptional regulation by the glucocorticoid receptor (GR) is essential for survival. Since the GR can influence transcription both through DNA-binding-dependent and -independent mechanisms, we attempted to assess their relative importance in vivo. In order to separate these modes of action, we introduced the point mutation A458T into the GR by gene(More)
The HNF-3 alpha, beta and gamma genes constitute a family of transcription factors that are required for hepatocyte-specific gene expression of a number of genes, e.g. transthyretin, alpha-1 antitrypsin and tyrosine aminotransferase. These genes share a highly conserved DNA-binding domain first found in the Drosophila gene, forkhead, which is required for(More)
Recent developments in next-generation sequencing have enabled whole-genome profiling of nucleosome organizations. Although several algorithms for inferring nucleosome position from a single experimental condition have been available, it remains a challenge to accurately define dynamic nucleosomes associated with environmental changes. Here, we report a(More)
We demonstrate that conditional ablation of the homeobox transcription factor Cdx2 from early endoderm results in the replacement of the posterior intestinal epithelium with keratinocytes, a dramatic cell fate conversion caused by ectopic activation of the foregut/esophageal differentiation program. This anterior homeotic transformation of the intestine was(More)
To define the role of cAMP signaling in gene control, we have generated mice with a mutation in the cAMP response element binding protein (CREB) gene. Mice carrying this mutation are viable but show an impairment in memory consolidation. In further analysis of these mice, we have found an up-regulation of a CREB isoform that has not been described(More)
BACKGROUND & AIMS Intestinal-type gastric cancer is often preceded by intestinal metaplasia in humans. The genetic events responsible for the transdifferentiation that occurs in intestinal metaplasia are not well understood. Cdx2, a transcription factor whose expression is normally limited to the intestine, has been detected in gastric intestinal(More)
Klf4 (formerly GKLF) is a zinc-finger transcription factor expressed in the epithelia of the skin, lungs, gastrointestinal tract and several other organs. In vitro studies have suggested that Klf4 plays an important role in cell proliferation and/or differentiation. Mice homozygous for a null mutation in Klf4 die within 15 hours of birth and show selective(More)