Methods and kits for quantifying adenosine-containing molecules within an aqueous composition. Particularly, the methods utilize a competitive fluorescence-polarization and FRET-based assays that directly measure the production of adenosine-containing compounds, particularly S-adenosylhomocysteine (AdoHcy) compounds produced by MTases. The generation of AdoHcy can be quantified by displacing a novel fluorescent probe comprising a 5-carboxytetramethylrhodamine fluorophore covalently bound to an adenosine scaffold from a catalytically inert 5-methylthioadenosine nucleosidase (MTAN) variant. One or more of the reaction materials can be pre-loaded into wells within multi-well reaction plates as a kit, which can be used to determine the enzymatic activity of MTases or conduct drug screening for potential inhibitors in a high-throughput format. Additionally, the developed assay is applicable to S-adenosyl methionine-dependent and adenosine triphosphate-dependent enzymes by detecting adenosine and various adenosine-containing molecules including 5-methylthioadenosine, adenosine monophosphate and adenosine diphosphate produced during the course of a chemical reaction.

The present disclosure relates to chemical compounds that inhibit HP1-mediated heterochromatin formation, pharmaceutical compositions containing such compounds, methods of identifying such compounds, and their use in the treatment of disorders related to heterochromatin formation such as, for example, a disorder of cellular proliferation (e.g., cancer). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Methods of determining suitability of a subject to be treated with a microtubule targeting agent (MTA) by measuring SETDB1 expression levels are provided. Methods of treating cancer by administering an MTA are also provided. Kits comprising agents for specific detection of SETDB1 are also provided.

The present invention relates to a marker that can be used as aging biomarker. More specifically, the present invention relates to the analysis of nucleolar size as a biomarker for aging and metabolic health and its relation to the virtual age, or the life expectancy of animals, including humans. The aging biomarker of the invention can be used to study the effect of medication, food compounds and/or special diets on the wellness and virtual age, or the life expectancy of animals, including humans.

The invention relates to inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, the catalytic subunit of the PRC2 complex which catalyzes the mono- through tri-methylation of lysine 27 on histone H3 (H3-K27). In one embodiment the inhibition is selective for the mutant form of the EZH2, such that trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The methods can be used to treat cancers including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying small molecule selective inhibitors of the mutant forms of EZH2 and also methods for determining responsiveness to an EZH2 inhibitor in a subject.

The invention provides methods of inhibiting epigenetic gene silencing in a cell expressing NPM/ALK or decreasing NPM/ALK content in a cell, by contacting a cell with an agent capable of increasing the concentration of Stat5a protein or its functional analog. Further, the invention provides a method of treating malignancies expressing oncogenic kinase by administering to a patient affected with a malignancy an agent capable of increasing the concentration of Stat5a protein or its epigenetically silenced functional tumor suppressor analog in a malignant cell. Finally, it provides a method to diagnose malignancy and monitor patient's response to therapy by analysis of the degree of DNA methylation of the gene encoding for Stat5a or its analog, their mRNA, or protein.

The invention features compositions and methods for a pre-cancer prognostic screen.

The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.

Methods and kits for quantifying adenosine-containing molecules within an aqueous composition. Particularly, the methods utilize a competitive fluorescence-polarization and FRET-based assays that directly measure the production of adenosine-containing compounds, particularly S-adenosylhomocysteine (AdoHcy) compounds produced by MTases. The generation of AdoHcy can be quantified by displacing a novel fluorescent probe comprising a 5-carboxytetramethylrhodamine fluorophore covalently bound to an adenosine scaffold from a catalytically inert 5-methylthioadenosine nucleosidase (MTAN) variant. One or more of the reaction materials can be pre-loaded into wells within multi-well reaction plates as a kit, which can be used to determine the enzymatic activity of MTases or conduct drug screening for potential inhibitors in a high-throughput format. Additionally, the developed assay is applicable to S-adenosyl methionine-dependent and adenosine triphosphate-dependent enzymes by detecting adenosine and various adenosine-containing molecules including 5-methylthioadenosine, adenosine monophosphate and adenosine diphosphate produced during the course of a chemical reaction.

The present invention relates to methods and pharmaceutical composition for the treatment of T-helper type 2 (Th2)-mediated diseases. More particularly, the present invention relates to an inhibitor of the Suv39h1-HP1a silencing pathway for use in the treatment of a T-helper type 2 (Th2)-mediated disease, in particular allergic asthma.