Degron Protease Blockade Sensor to Image Epigenetic Histone Protein Methylation in Cells and Living Animals | Zendy

Thillai V. Sekar | Zendy; Kira Foygel | Zendy; Rammohan Devulapally | Zendy; Ramasamy Paulmurugan | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

Degron Protease Blockade Sensor to Image Epigenetic Histone Protein Methylation in Cells and Living Animals

Author(s) -

Thillai V. Sekar,

Kira Foygel,

Rammohan Devulapally,

Ramasamy Paulmurugan

Publication year - 2014

Publication title -

acs chemical biology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.899

H-Index - 111

eISSN - 1554-8937

pISSN - 1554-8929

DOI - 10.1021/cb5008037

Subject(s) - methyltransferase , histone h3 , methylation , epigenetics , in vivo , biology , histone , histone methyltransferase , microbiology and biotechnology , histone methylation , drug development , drug discovery , cancer research , dna methylation , computational biology , pharmacology , biochemistry , drug , genetics , gene expression , dna , gene

Lysine methylation of histone H3 and H4 has been identified as a promising therapeutic target in treating various cellular diseases. The availability of an in vivo assay that enables rapid screening and preclinical evaluation of drugs that potentially target this cellular process will significantly expedite the pace of drug development. This study is the first to report the development of a real-time molecular imaging biosensor (a fusion protein, [FLuc2]-[Suv39h1]-[(G4S)3]-[H3-K9]-[cODC]) that can detect and monitor the methylation status of a specific histone lysine methylation mark (H3-K9) in live animals. The sensitivity of this sensor was assessed in various cell lines, in response to down-regulation of methyltransferase EHMT2 by specific siRNA, and in nude mice with lysine replacement mutants. In vivo imaging in response to a combination of methyltransferase inhibitors BIX01294 and Chaetocin in mice reveals the potential of this sensor for preclinical drug evaluation. This biosensor thus has demonstrated its utility in the detection of H3-K9 methylations in vivo and potential value in preclinical drug development.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research