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Direct genomic manipulation at a specific locus is still not feasible in most vertebrate model organisms. In vertebrate cell lines, genomic lesions at a specific site have been introduced using zinc-finger nucleases (ZFNs). Here we adapt this technology to create targeted mutations in the zebrafish germ line. ZFNs were engineered that recognize sequences in(More)
BACKGROUND Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) or ChIP followed by genome tiling array analysis (ChIP-chip) have become standard technologies for genome-wide identification of DNA-binding protein target sites. A number of algorithms have been developed in parallel that allow identification of binding sites(More)
Aging research has been very successful at identifying signaling pathways and evolutionarily conserved genes that extend lifespan with the assumption that an increase in lifespan will also increase healthspan. However, it is largely unknown whether we are extending the healthy time of life or simply prolonging a period of frailty with increased incidence of(More)
Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding family of transcription factors, which compose a large group of basic region leucine zipper proteins whose members mediate diverse transcriptional regulatory functions. ATF5 has a well-established prosurvival activity and has been found to be overexpressed in(More)
Activating transcription factor-5 (ATF5) is highly expressed in malignant glioma and has a key role in promoting cell survival. Here we perform a genome-wide RNAi screen to identify transcriptional regulators of ATF5. Our results reveal an essential survival pathway in malignant glioma, whereby activation of a RAS-mitogen-activated protein kinase or(More)
Neurodegenerative disorders share a process of aggregation of insoluble protein. Frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) is characterized by the presence of ubiquitin and TDP-43 positive aggregates which are likely related to specific gene expression profiles. We carried out gene expression microarray analysis on post-mortem(More)
CRISPR-Cas systems are a diverse family of RNA-protein complexes in bacteria that target foreign DNA sequences for cleavage. Derivatives of these complexes have been engineered to cleave specific target sequences depending on the sequence of a CRISPR-derived guide RNA (gRNA) and the source of the Cas9 protein. Important considerations for the design of(More)
Endoplasmic reticulum (ER) stress-mediated cell death has an important role in the pathogenesis of chronic diseases, including diabetes and neurodegeneration. Although proapoptotic programs activated by ER stress have been extensively studied, identification and characterization of antiapoptotic programs that counteract ER stress are currently incomplete.(More)
Epigenetic regulation and interactions between transcription factors and regulatory genomic regions play crucial roles in controlling transcriptional regulatory networks that drive development, environmental responses, and disease. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) and ChIP followed by genomic tiling(More)
FlyFactorSurvey (http://pgfe.umassmed.edu/TFDBS/) is a database of DNA binding specificities for Drosophila transcription factors (TFs) primarily determined using the bacterial one-hybrid system. The database provides community access to over 400 recognition motifs and position weight matrices for over 200 TFs, including many unpublished motifs. Search(More)