Project description:During mammalian spermiogenesis, the majority of the nucleosomes packaging the male haploid genome are replaced by protamines to produce a highly compact chromatin architecture that is critical to male fertility. We have carried out a genomewide survey of murine spermatozoal chromatin using a micrococal nuclease approach to characterise the DNA sequences that remain packaged by histones.
Project description:During mammalian spermiogenesis, the majority of the nucleosomes packaging the male haploid genome are replaced by protamines to produce a highly compact chromatin architecture that is critical to male fertility. We have carried out a genomewide survey of human spermatozoal chromatin using both a salt and micrococal nuclease approach to characterise the DNA sequences that remain packaged by histones.
Project description:The replication timing program, or the order in which DNA is duplicated during S-phase, is associated with various features of chromosome structure and function, including gene expression, histone modifications, and 3-D compartmentalization of chromatin.
Project description:We found that BAP1 (BRCA1 Associated Protein-1) shows loss of heterozygosity in over 25% of pancreatic cancer patients and functions as tumor suppressor. Conditional deletion of Bap1 in murine pancreas led to genomic instability, accumulation of DNA damage, and an inflammatory response that evolved to pancreatitis with full penetrance. Concomitant expression of oncogenic KrasG12D led to malignant transformation and development of invasive and metastatic pancreatic cancer. At the molecular level, BAP1 maintains the integrity of the exocrine pancreas by regulating genomic stability and its loss confers sensitivity to radio- and platinum-based therapies.
Project description:The importance of unanchored Ub in innate immunity has been shown only for a limited number of unanchored Ub-interactors. We investigated what additional cellular factors interact with unanchored Ub and whether unanchored Ub plays a broader role in innate immunity. To identify unanchored Ub-interacting factors from murine lungs, we used His-tagged recombinant poly-Ub chains as bait. These chains were mixed with lung tissue lysates and protein complexes were isolated with Ni-NTA beads. Sample elutions were subjected to mass spectrometry (LC-MSMS) analysis.