Epigenetics of Alzheimer's disease and frontotemporal dementia.

This article will review the recent advances in the understanding of the role of epigenetic modifications and the promise of future epigenetic therapy in neurodegenerative dementias, including Alzheimer's disease and frontotemporal dementia.

The UBC9 E2 SUMO conjugating enzyme binds the PR-Set7 histone methyltransferase to facilitate target gene repression.

PR-Set7/Set8/KMT5a is a chromatin-modifying enzyme that specifically monomethylates lysine 20 of histone H4 (H4K20me1). In this study we attempted to identify PR-Set7-interacting proteins reasoning that these proteins would provide important insights into the role of PR-Set7 in transcriptional regulation. Using an unbiased yeast two-hybrid approach, we discovered that PR-Set7 interacts with the UBC9 E2 SUMO conjugating enzyme.

Role for the nuclear receptor-binding SET domain protein 1 (NSD1) methyltransferase in coordinating lysine 36 methylation at histone 3 with RNA polymerase II function.

The NSD (nuclear receptor-binding SET domain protein) family encodes methyltransferases that are important in multiple aspects of development and disease. Perturbations in NSD family members can lead to Sotos syndrome and Wolf-Hirschhorn syndrome as well as cancers such as acute myeloid leukemia. Previous studies have implicated NSD1 (KMT3B) in transcription and methylation of histone H3 at lysine 36 (H3-K36), but its molecular mechanism in these processes remains largely unknown.

PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression.

Increasing evidence indicates that the post-translational modifications of the histone proteins play critical roles in all eukaryotic DNA-templated processes. To gain further biological insights into two of these modifications, the mono- and trimethylation of histone H4 lysine 20 (H4K20me1 and H4K20me3), ChIP-chip experiments were performed to identify the precise genomic regions on human chromosomes 21 and 22 occupied by these two modifications. Detailed analysis revealed that H4K20me1 was preferentially enriched within specific genes; most significantly between the first approximately 5% and 20% of gene bodies.

Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi.

Background: The evolution of multicellularity is accompanied by the occurrence of differentiated tissues, of organismal developmental programs, and of mechanisms keeping the balance between proliferation and differentiation. Initially, the SET-domain proteins were associated exclusively with regulation of developmental genes in metazoa. However, finding of SET-domain genes in the unicellular yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe suggested that SET-domain proteins regulate a much broader variety of biological programs.