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A novel 15-subunit complex with the capacity to remodel the structure of chromatin, termed RSC, has been isolated from S. cerevisiae on the basis of homology to the SWI/SNF complex. At least three RSC subunits are related to SWI/SNF polypeptides: Sth1p, Rsc6p, and Rsc8p are significantly similar to Swi2/Snf2p, Swp73p, and Swi3p, respectively, and were identified by mass spectrometric and sequence...
Vascular endothelial growth factor (VEGF), which acts via members of a family of endothelial-specific receptor tyrosine kinases, is the only factor that has been shown definitively to play a role in the formation of the embryonic vasculature. Only one other family of receptor tyrosine kinases, comprising TIE1 and TIE2, is largely endothelial cell specific. We have recently cloned a ligand for TIE2,...
Integration host factor (IHF) is a small heterodimeric protein that specifically binds to DNA and functions as an architectural factor in many cellular processes in prokaryotes. Here, we report the crystal structure of IHF complexed with 35 bp of DNA. The DNA is wrapped around the protein and bent by >160°, thus reversing the direction of the helix axis within a very short distance. Much of the...
Venous malformations (VMs), the most common errors of vascular morphogenesis in humans, are composed of dilated, serpiginous channels. The walls of the channels have a variable thickness of smooth muscle; some mural regions lack smooth muscle altogether. A missense mutation resulting in an arginine-to-tryptophan substitution at position 849 in the kinase domain of the receptor tyrosine kinase TIE2...
X-MyT1 is a C2HC-type zinc finger protein that we find to be involved in the primary selection of neuronal precursor cells in Xenopus. Expression of this gene is positively regulated by the bHLH protein X-NGNR-1 and negatively regulated by the Notch/Delta signal transduction pathway. X-MyT1 is able to promote ectopic neuronal differentiation and to confer insensitivity to lateral inhibition, but only...
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors. We previously reported that transcriptional activation of hunchback (hb) and huckebein(hkb) by Bicoid in the Drosophila embryo is impaired by mutations in TAFII110 and TAFII60. This conclusion was based on...
In a screen for genes that interact with the Rap1 GTPase, we have identified a Drosophila gene, dacapo (dap), which is a member of the p21/p27 family of cdk inhibitors. Unlike mammalian cdk inhibitors studied to date, dap is essential for normal embryonic development. Dacapo inhibits cyclin-cdk activity in vitro. Overexpressing dap during eye development interferes with cell cycle progression and...
To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca 2+ -independent form of CaM Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but they lack LTP in response to stimulation at 5–10 Hz and are impaired on spatial...
The molecular mechanism by which bacterial avirulence genes mediate recognition by resistant host plants has been enigmatic for more than a decade. In this paper we provide evidence that the Xanthomonas campestris pv. vesicatoria avirulence protein AvrBs3 is recognized inside the plant cell. Transient expression of avrBs3 in pepper leaves, using Agrobacterium tumefaciens for gene delivery, results...
To investigate the role of synaptic plasticity in the place-specific firing of the hippocampus, we have applied multiple electrode recording techniques to freely behaving mice with a CA1 pyramidal cell–specific knockout of the NMDAR1 gene. We have discovered that although the CA1 pyramidal cells of these mice retain place-related activity, there is a significant decrease in the spatial specificity...
While changes in gene expression are critical for many brain functions, including long-term memory, little is known about the cellular processes that mediate stimulus–transcription coupling at central synapses. In studying the signaling pathways by which synaptic inputs control the phosphorylation state of cyclic AMP–responsive element binding protein (CREB) and determine expression of CRE-regulated...
Most cell types in multicellular eukaryotes exit from the mitotic cell cycle before terminal differentiation. We show that the dacapo gene is required to arrest the epidermal cell proliferation at the correct developmental stage during Drosophila embryogenesis. dacapo encodes an inhibitor of cyclin E/cdk2 complexes with similarity to the vertebrate Cip/Kip inhibitors. dacapo is transiently expressed...
Summary We have produced a mouse strain in which the deletion of the NMDAR1 gene is restricted to the CA1 pyramidal cells of the hippocampus by using a new and general method that allows CA1-restricted gene knockout. The mutant mice grow into adulthood without obvious abnormalities. Adult mice lack NMDA receptor–mediated synaptic currents and long-term potentiation in the CA1 synapses and exhibit...
The transcription initiation factor TFIID is a multimeric protein complex composed of TATA box–binding protein (TBP) and many TBP-associated factors (TAF II s). TAF II s are important cofactors that mediate activated transcription by providing interaction sites for distinct activators. Here, we present evidence that human TAF II 250 and its homologs in Drosophila and yeast...
MAD-related (MADR) proteins are essential intracellular components of TGFβ signaling pathways and are regulated by phosphorylation. Here, we demonstrate that MADR2 and not the related protein DPC4 transiently interacts with the TGFβ receptor and is directly phosphorylated by the complex on C-terminal serines. Interaction of MADR2 with receptors and phosphorylation requires activation of receptor I...
Using the phage P1–derived Cre/loxP recombination system, we have developed a method to create mice in which the deletion (knockout) of virtually any gene of interest is restricted to a subregion or a specific cell type in the brain such as the pyramidal cells of the hippocampal CA1 region. The Cre/loxP recombination–based gene deletion appears to require a certain level of Cre protein expression...
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