Methods for identifying a test agent as a modulator of the active DNA demethylation activity of a DNA methyltransferase are disclosed. The method comprises: a) providing a methylated DNA; b) providing the DNA methyltransferase; c) allowing the methylated DNA to react with the DNA methyltransferase for a sufficient time to perform a demethylation reaction and generate a demethylated DNA product in the presence or absence of a test agent; d) analyzing the extent of demethylation; and d) comparing the extents of the demethylation in the presence and absence of the test agent, and thereby identify the test agent as a modulator of the DNA demethylation activity of the DNA methyltransferase.

Provided herein are methods for diagnosing cancer by determining the level of expression of SETDB1 in a biological sample. Also provided herein are methods for treating cancer by administering an inhibitor of SETDB1 to a subject in need thereof.

The instant invention relates to methods for the treatment of WEE1 kinase associated cancer by administering a WEE1 inhibitor, wherein the WEE1 inhibitor is WEE1-1 or a pharmaceutically acceptable salt thereof, or WEE1-2 or a pharmaceutically acceptable salt thereof. In another embodiment, the invention relates to a method for treating a WEE1 kinase associated cancer patient, comprising administering a WEE1 inhibitor, wherein the cancer cells of said patient to be treated are characterized by low expression levels of PKMYT1.

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 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 present invention relates to targeted conversion of alpha-hydroxyalkylated residues in biomolecules in the presence of a directing methyltransferase, namely to targeted removal of the alpha-hydroxyalkyl moieties to give unmodified residues, or targeted derivatization of the alpha-hydroxyalkyl groups by covalent coupling of non-cofactor compounds represented by formula HQ-LX, wherein X represents a functional group or a reporter group attached via a linker moiety L, and QH is selected from HS, HSe, HOH.sub.2N, HN.sub.3 or HCN in the presence of a directing methyltransferase. Further development of the method of targeted conversion comprises methods for targeted labeling a biomolecule and method for detecting hydroxymethylated target sites in a biomolecule according to the present invention.

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 present invention provides an in vitro directed evolution selection system to create modified methyltransferases which improve methyltransferase specificity and use it to optimize and provide fusion proteins comprising a zinc finger methyltransferase derived from M.SssI. The resulting fusion proteins show increased target methylation specificity and greatly decreased non-target methylation compared to wild-type enzyme activity. Methods of use of such fusion proteins in both prokaryotic and eukaryotic cells are also provided.

A method for identification of a multipotent mesenchymal stem cell subpopulation, among a heterogenic population of gastrointestinal tract mucosa mesenchymal stromal cells, is provided. Further provided is a kit including a probe for identification or isolation of gastrointestinal tract mucosa mesenchymal stem cells, and a pharmaceutical composition including enriched or isolated mesenchymal stem cell from the gastrointestinal tract mucosa, for treating an individual suffering from a disorder or a disease.

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.