labeling of endogenous genomic loci in using CRISPR/dCas9.

Visualization of genomic loci with open chromatin state has been reported in mammalian tissue culture cells using a CRISPR/Cas9-based system that utilizes an EGFP-tagged endonuclease-deficient Cas9 protein (dCas9::EGFP) (Chen et al. 2013). Here, we adapted this approach for use in .

Genome-wide RNAi screen for regulators of UPRmt in Caenorhabditis elegans mutants with defects in mitochondrial fusion.

Mitochondrial dynamics plays an important role in mitochondrial quality control and the adaptation of metabolic activity in response to environmental changes. The disruption of mitochondrial dynamics has detrimental consequences for mitochondrial and cellular homeostasis and leads to the activation of the mitochondrial unfolded protein response (UPRmt), a quality control mechanism that adjusts cellular metabolism and restores homeostasis. To identify genes involved in the induction of UPRmt in response to a block in mitochondrial fusion, we performed a genome-wide RNAi screen in Caenorhabditis elegans mutants lacking the gene fzo-1, which encodes the ortholog of mammalian Mitofusin, and identified 299 suppressors and 86 enhancers.

miRNAs cooperate in apoptosis regulation during development.

Programmed cell death occurs in a highly reproducible manner during development. We demonstrate that, during embryogenesis, miR-35 and miR-58 family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene , which encodes a proapoptotic BH3-only protein. In addition, we present evidence that repression of is dependent on binding sites for miR-35 and miR-58 family miRNAs within the 3' untranslated region (UTR), which affect both mRNA copy number and translation.

P-value-based regulatory motif discovery using positional weight matrices.

To analyze gene regulatory networks, the sequence-dependent DNA/RNA binding affinities of proteins and noncoding RNAs are crucial. Often, these are deduced from sets of sequences enriched in factor binding sites. Two classes of computational approaches exist.

The XXmotif web server for eXhaustive, weight matriX-based motif discovery in nucleotide sequences.

The discovery of regulatory motifs enriched in sets of DNA or RNA sequences is fundamental to the analysis of a great variety of functional genomics experiments. These motifs usually represent binding sites of proteins or non-coding RNAs, which are best described by position weight matrices (PWMs). We have recently developed XXmotif, a de novo motif discovery method that is able to directly optimize the statistical significance of PWMs.