Jana P Lim

Stanford University | SU · Department of Genetics

Prkcz has been identified as a gene whose expression is positively correlated with ethanol (EtOH) consumption in mice and is also induced by EtOH. Two proteins are produced from Prkcz: protein kinase M zeta (PKMζ), which is expressed in the nervous system and protein kinase C zeta (PKCζ), which is expressed in other tissues. We examined Prkcz(-/-)...

The maize (Zea mays) RNA Polymerase IV (Pol IV) largest subunit, RNA Polymerase D1 (RPD1 or NRPD1), is required for facilitating paramutations, restricting expression patterns of genes required for normal development, and generating small interfering RNA (siRNAs). Despite this expanded role for maize Pol IV relative to Arabidopsis thaliana, neither...

It is textbook knowledge that inheritance of traits is governed by genetics, and that the epigenetic modifications an organism acquires are largely reset between generations. Recently, however, transgenerational epigenetic inheritance has emerged as a rapidly growing field, providing evidence suggesting that some epigenetic changes result in persis...

Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP)...

Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the...

Despite recent advances in the understanding of ethanol's biological action, many of the molecular targets of ethanol and mechanisms behind ethanol's effect on behavior remain poorly understood. In an effort to identify novel genes, the products of which regulate behavioral responses to ethanol, we recently identified a mutation in the dtao gene th...

The CRF (corticotropin-releasing factor) system is a key mediator of the stress response. Alterations in CRF signaling have been implicated in drug craving and ethanol consumption. The development of negative reinforcement via activation of brain stress systems has been proposed as a mechanism that contributes to alcohol dependence. Here, we isolat...

Meiotically heritable epigenetic changes in gene regulation known as paramutations are facilitated by poorly understood trans-homolog interactions. Mutations affecting paramutations in maize (Zea mays) identify components required for the accumulation of 24-nucleotide RNAs. Some of these components have Arabidopsis thaliana orthologs that are part...

Although genetic background alters responses to ethanol, there has not yet been a methodical quantification of differences in ethanol-related behaviors between inbred and hybrid mice commonly used in gene-targeting studies. Here, we compared C57BL/6NTac × 129S6/SvEvTac F1 hybrid mice (B6129S6) with C57BL/6NTac inbred mice (B6NT), and C57BL/6J × 129...

Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendants. The histone H3 lysine 4 trimethylation (H3K4me3) complex, composed of ASH-2, WDR-5 and the histon...

Transcripts showing significantly altered expression in dLmo mutants EP1306 and BxJ. Columns (from left to right) indicate the Affymetrix probe set identifier, the gene symbol, the FlyBase annotation, the cluster number from HOPACH clustering, the mean expression value of the transcript (normalized to expression in control w;iso flies and expressed...

Flies carrying the MB06458 insertion do not show altered ethanol absorption. For each sample, 25 male control and MB06458 flies were exposed for 15 min to ethanol at a dose of 100∶50 (ethanol vapor∶air) and immediately frozen. Ethanol concentration was measured using a NAD∶ADH enzymatic assay on homogenized flies. Shown is the % ethanol concentrati...

Increased MEK phosphorylation in the striatum of AlkKO mice. Striatum was dissected from the brains of adult male mice and analyzed using the PathScan® Phospho-MEK1 and Total MEK1 Sandwich ELISA kits from Cell Signaling Technology. Shown is the ratio of phosphorylated MEK to total MEK (pMEK/MEK) in wild-type (+/+) and AlkKO (−/−) mice. *P = 0.005 b...

Generation of AlkKO mice. (A) Scheme for generating AlkKO mice. An EcoRI fragment of the Alk genomic DNA locus was used to develop the Alk targeting vector, in which the exons coding for juxtamembrane domain of the ALK protein and the ATP binding pocket of the kinase domain, and their flanking sequences were replaced by a neo expression cassette. A...

Anaplastic lymphoma kinase (Alk) is a gene expressed in the nervous system that encodes a receptor tyrosine kinase commonly known for its oncogenic function in various human cancers. We have determined that Alk is associated with altered behavioral responses to ethanol in the fruit fly Drosophila melanogaster, in mice, and in humans. Mutant flies c...

Alignment of full-length NRPD2 proteins from diverse plant species. Full-length NRPD2 proteins were aligned using MAFFT and edited using GeneDoc. Shading represents 60% (lightest), 80%, and 100% (darkest) sequence conservation. Conserved domains are highlighted below the text, and NRPD2a lesions are indicated by underlined text. (0.39 MB PDF)

Oligonucleotide primers used for nrpd2a sequencing. Oligonucleotide primers designed to amplify the predicted coding regions of the nrpd2a-like gene candidate from genomic DNA sequence by PCR. (0.04 MB DOC)

Author Summary Multicellular plants possess a unique set of DNA–dependent RNA polymerase complexes (RNAPs) that prevent certain repetitious regions of the genome from being copied into stable RNAs. Two distinct RNAPs, termed Pol IV and Pol V, are required for this type of genome-silencing behavior in the eudicot Arabidopsis thaliana, but the mechan...

Plants have distinct RNA polymerase complexes (Pol IV and Pol V) with largely unknown roles in maintaining small RNA-associated gene silencing. Curiously, the eudicot Arabidopsis thaliana is not affected when either function is lost. By use of mutation selection and positional cloning, we showed that the largest subunit of the presumed maize Pol IV...