Chromatin regulation in schistosomes and histone modifying enzymes as drug targets

Chromatin regulation in schistosomes and histone modifying enzymes as drug targets.

Only one drug is currently available for the treatment and control of schistosomiasis and the increasing risk of selecting strains of schistosome that are resistant to praziquantel means that the development of new drugs is urgent. With this objective we have chosen to target the enzymes modifying histones and in particular the histone acetyltransferases and histone deacetylases (HDAC). Inhibit...

SnapShot: Histone-Modifying Enzymes

Co-Regulation of Histone-Modifying Enzymes in Cancer

Cancer is characterized by aberrant patterns of expression of multiple genes. These major shifts in gene expression are believed to be due to not only genetic but also epigenetic changes. The epigenetic changes are communicated through chemical modifications, including histone modifications. However, it is unclear whether the binding of histone-modifying proteins to genomic regions and the plac...

Chromatin-modifying enzymes in transcription and cancer

In recent years, our view of how gene expression is controlled has changed dramatically. The discovery of enzymes that modify histones has revealed that transcription is an enzymically driven process. Such modifications can recruit specific proteins and mediate chromatin changes that affect transcription either positively or negatively. Important biological pathways leading to cell proliferatio...

Coordinated recruitment of histone methyltransferase G9a and other chromatin-modifying enzymes in SHP-mediated regulation of hepatic bile acid metabolism.

SHP has been implicated as a pleiotropic regulator of diverse biological functions by its ability to inhibit numerous nuclear receptors. Recently, we reported that SHP inhibits transcription of CYP7A1, a key gene in bile acid biosynthesis, by recruiting histone deacetylases (HDACs) and a Swi/Snf-Brm complex. To further delineate the mechanism of this inhibition, we have examined whether methyla...