ABSTRACT
The PEV-modifying winged-helix/forkhead domain transcription factor JUMU of Drosophila is an essential protein of pleiotropic function. The correct gene dose of jumu is required for nucleolar integrity and correct nucleolus function. Overexpression of jumu results in bloating of euchromatic chromosome arms, displacement of the JUMU protein from the chromocenter and the nucleolus, fragile weak points, and disrupted chromocenter of polytene chromosomes. Overexpression of the acidic C terminus of JUMU alone causes nucleolus disorganization. In addition, euchromatic genes are overexpressed and HP1, which normally accumulates in the pericentric heterochromatin and spreads into euchromatic chromosome arms, although H3-K9 di-methylation remains restricted to the pericentric heterochromatin. The human winged-helix nude gene shows similarities to jumu and its overexpression in Drosophila causes bristle mutations.
Subject(s)
Cell Nucleolus/metabolism , Chromatin/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/growth & development , Drosophila melanogaster/metabolism , Transcription Factors/metabolism , Amino Acid Sequence , Animals , Cell Nucleolus/genetics , Drosophila Proteins/chemistry , Drosophila Proteins/genetics , Larva/metabolism , Microscopy, Confocal , Molecular Sequence Data , Protein Binding , Protein Transport , Salivary Glands/cytology , Salivary Glands/metabolism , Transcription Factors/chemistry , Transcription Factors/genetics , Transcription, GeneticABSTRACT
Reversible epigenetic changes that alter gene expression are a characteristic of many cancers and other diseases. Biotech companies are taking note and are starting to develop new drugs to reverse such pathogenic "epimutations."
Subject(s)
Chromatin Assembly and Disassembly/drug effects , Epigenesis, Genetic , Neoplasms/drug therapy , DNA Methylation , Gene Expression Regulation , Histone Deacetylase Inhibitors/therapeutic use , HumansABSTRACT
The global financial crisis has hit biotech companies hard both in the US and Europe as venture capital dries up. Finding new sources of long-term financing for translating research into new therapeutics will be essential for maintaining innovation and new drug development by biotech companies.
