HD2 proteins are plant specific histone deacetylases. Four HD2 proteins, HD2A, HD2B, HD2C, and HD2D, have been identified in Arabidopsis. It was found that the expression of HD2A, HD2B, HD2C, and HD2D was repressed by ABA and NaCl. To investigate the function of HD2 proteins further, two HD2C T-DNA insertion lines of Arabidopsis, hd2c-1 and hd2c-3 were identified. Compared with wild-type plants, hd2c-1 and hd2c-3 plants displayed increased sensitivity to ABA and NaCl during germination and decreased tolerance to salt stress. These observations support a role of HD2C in the ABA and salt-stress response in Arabidopsis. Moreover, it was demonstrated that HD2C interacted physically with a RPD3-type histone deacetylase, HDA6, and bound to histone H3. The expression of ABA-responsive genes, ABI1 and ABI2, was increased in hda6, hd2c, and hda6/hd2c-1 double mutant plants, which was associated with increased histone H3K9K14 acetylation and decreased histone H3K9 dimethylation. Taken together, our results suggested that HD2C functionally associates with HDA6 and regulates gene expression through histone modifications.

Delivery technologies for the CRISPR-Cas9 gene editing system often require viral vectors, which pose safety concerns for therapeutic genome editing 1. Alternatively, cationic liposomal components or polymers can be used to encapsulate multiple CRISPR components into large particles (typically >100 nm diameter); however, such systems are limited by variability in loading of the cargo. Here, we report the design of customizable synthetic nanoparticles for the delivery of Cas9 nuclease and a single-guide RNA (sgRNA), enabling controlled stoichiometry of CRISPR components and limiting possible safety concerns in vivo. We describe the synthesis of a thin Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Histone modifications play an important role in the epigenetic regulation of gene expression. All histone modifications are reversible, which may therefore provide a flexible way for regulating gene expression during the plant's development and during the plant response to environmental stimuli. The reversible acetylation and deacetylation of specific lysine residues on core histones are catalysed by histone acetyltransferases and histone deacetylases (HDAs). HDA6 is an RPD3-type histone deacetylase in Arabidopsis. The Arabidopsis HDA6 mutant, axe1-5, and HDA6 RNA-interfering plants displayed a phenotype that was hypersensitive to ABA and salt stress. Compared with wild-type plants, the expression of the ABA and abiotic stress-responsive genes, ABI1, ABI2, KAT1, KAT2, DREB2A, RD29A, and RD29B, was decreased in axe1-5 and HDA6 RNA-interfering plants when treated with ABA or salt stress. It was found that both ABA and salt stress could enrich the gene activation markers, histone H3K9K14 acetylation, and H3K4 trimethylation, but decrease the gene repression marker, H3K9 dimethylation, of the ABA and abiotic stress-responsive genes. Our study indicates that HDA6-involved histone modifications modulate seed germination and the salt stress response, as well as ABA- and salt stress-induced gene expression in Arabidopsis.

Metabolic reprogramming is a hallmark of cancer. Herein we discovered that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondria calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol 1, 4, 5-trisphosphate receptors (IP3Rs), methylated PKM2 inhibits the influx of calcium from endoplasmic reticulum (ER) to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticle perturbs metabolic energy balance in cancer cells, leading to decrease of cell proliferation, migration, and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to IP3R-dependent mitochondrial functions.