Background We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Results Methylome analysis from peripheral blood samples of six... Show moreBackground We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Results Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. Conclusions We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis. Show less
Smeenk, G.; Wiegant, W.W.; Marteijn, J.A.; Luijsterburg, M.S.; Sroczynski, N.; Costelloe, T.; ... ; Attikum, H. van 2013
Agrobacterium is the natures genetic engineer that can transfer genes across the kingdom barriers to both prokaryotic and eukaryotic host cells. The host genes which are involved in Agrobacterium... Show moreAgrobacterium is the natures genetic engineer that can transfer genes across the kingdom barriers to both prokaryotic and eukaryotic host cells. The host genes which are involved in Agrobacterium-mediated transformatiom (AMT) are not well known. Here, I studied in a systematic way to identify the whole eukaryotic host genes which are involved in this event. For this, I used a collection of around 4800 homozygous diploid deletion mutants and the cDNA libraries of yeast Saccharomyces cerevisiae as the eukaryotic host and two strains of Agrobacterium. First, a large-scale AMT protocol for the transformation of yeast mutants was developed. Then, the yeast mutant collection was screened for the mutants with an increased or a decreased AMT. 249 deletion mutant strains were found which affect AMT. Of great importance were host chromatin remodeling and histone modifying complexes. Besides, using GFP technique I showed the nuclear localization of Agrobacteriums VirD2 in yeast. Yeast two-hybrid screens also identified 12 yeast putative interaction partners of VirD2 protein. Show less
