The University of North Carolina at Chapel Hill

Children's Medical Center Corporation

Boston University

Yi Zhang

Qin Feng

Yuki Okada

Ji-Xin Cheng

Shogo Matoba

Guoliang Xu

Cheng Zong

Hengbin Wang

Ru Cao

Azusa Inoue

Robert John Klose

Yuichi Tsukada

Kenichi Yamane

The invention provides methods for activating a repressed allele within an imprinting control region, thereby treating an imprinting associated disorder.

Compositions and methods for treating diseases associated with an imprinting defect

Microscopic analysis of a sample includes a fluorescent dye disposed within the sample. A mid-IR optical source generates a mid-infrared beam, which is directed onto the sample to induce a temperature change by absorption of the mid-infrared beam. An optical source generates a probe beam directed to impinge on the sample. A detector detects fluorescent emissions from the sample when the probe beam impinges on the sample. A data acquisition and processing system acquires and processes the detected fluorescent emissions from the sample to: (i) generate a signal indicative of infrared absorption by the sample, (ii) generate a signal indicative of temperature in the sample based on the signal indicative of infrared absorption by the sample, (iii) generate an image of the sample using the signal indicative of temperature in the sample.

Fluorescence-coded mid-infrared photothermal microscope

The present invention provides methods and compostions to improve the efficiency of somatic cell nuclear transfer (SCNT) and the consequent production of nuclear transfer ESC (ntESC) and transgenic cells and/or non-human animals. More specifically, the present invention relates to the discovery that trimethylation of Histone H3-Lysine 9 (H3K9me3) in reprogramming resistant regions (RRRs) in the nuclear genetic material of donor somatic cells prevents efficient somatic cell nuclear reprogramming or SCNT. The present invention provide methods and compositions to decrease H3K9me3 in methods to improve efficacy of SCNT by exogenous or overexpression of the demethylase Kdm4 family and/or inhibiting methylation of H3K9me3 by inhibiting the histone methyltransferases Suv39h1 and/or Suv39h2.

Methods and compositions to increase somatic cell nuclear transfer (SCNT) efficiency by removing histone H3-lysine trimethylation

The present invention provides polypeptides with histone H3 lysine 79 methyltransferase activity as well as nucleic acids encoding the same. Also provided are methods of using the polypeptides and nucleic acids of the invention in screening assays to identify compounds of interest. Further provided are diagnostic methods for leukemia and prognostic methods to predict the course of the disease in a subject.

DOT1 histone methyltransferases as a target for identifying therapeutic agents for leukemia

The present invention relates to methods of identifying candidate compounds for the treatment of leukemia and diagnostic methods based on histone methylation and HoxA5 promoter activity.

Diagnostic and therapeutic targets for leukemia

The present invention provides a native or reconstituted complex comprising Bmi1 and/or Ring1 and/or Ring2, wherein the complex has ubiquitin E3 ligase activity. Optionally, the complex further comprises HPH2 and/or HPC3. Also disclosed are methods of producing the reconstituted complex, methods of identifying compounds that modulate the ubiquitin E3 ligase activity of the native or reconstituted complex, and methods of identifying candidate compounds for treating cancer. Kits for determining modulation of protein ubiquitination and/or for ubiquitinating a target substrate are further provided.

Ubiquitin E3 ligase

The present invention provides a reconstituted complex including EED, EZH2 and SUZ12 wherein the reconstituted complex has histone methyltransferase (HMTase) activity for lysine 27 of histone H3 (H3-K27). The reconstituted complex may further include RbAp48, AEBP2 or both. Also disclosed are methods of producing the reconstituted complex, methods of identifying compounds that inhibit the HTMase activity of the reconstituted complex and methods of identifying candidate compounds for treating cancer. Reagents and kits including the reconstituted complex are further provided.

Growing community of inventors

Chapel Hill, NC, United States of America

Yi Zhang