SETDB1 activity is globally directed by H3K14 acetylation via its Triple Tudor Domain.

SETDB1 (SET domain bifurcated histone lysine methyltransferase 1) is a major protein lysine methyltransferase trimethylating lysine 9 on histone H3 (H3K9) which is involved in heterochromatin formation and silencing of repeat elements (REs). It contains a unique Triple Tudor Domain (3TD), which specifically binds the dual modification of H3K14ac in the presence of H3K9me1/2/3. Here, we explored the role of the 3TD H3-tail interaction for the H3K9 methylation activity of SETDB1.

Integrated epigenomic exposure signature discovery.

The epigenome influences gene regulation and phenotypes in response to exposures. Epigenome assessment can determine exposure history aiding in diagnosis. Here we developed and implemented a machine learning algorithm, the exposure signature discovery algorithm (ESDA), to identify the most important features present in multiple epigenomic and transcriptomic datasets to produce an integrated exposure signature (ES).

Distinct specificities of the HEMK2 protein methyltransferase in methylation of glutamine and lysine residues.

The HEMK2 protein methyltransferase has been described as glutamine methyltransferase catalyzing ERF1-Q185me1 and lysine methyltransferase catalyzing H4K12me1. Methylation of two distinct target residues is unique for this class of enzymes. To understand the specific catalytic adaptations of HEMK2 allowing it to master this chemically challenging task, we conducted a detailed investigation of the substrate sequence specificities of HEMK2 for Q- and K-methylation.

Genome-wide deposition of 6-methyladenine in human DNA reduces the viability of HEK293 cells and directly influences gene expression.

While cytosine-C5 methylation of DNA is an essential regulatory system in higher eukaryotes, the presence and relevance of 6-methyladenine (m6dA) in human cells is controversial. To study the role of m6dA in human DNA, we introduced it in human cells at a genome-wide scale at GANTC and GATC sites by expression of bacterial DNA methyltransferases and observed concomitant reductions in cell viability, in particular after global GANTC methylation. We identified several genes that are directly regulated by m6dA in a GANTC context.

Successful nephrectomy after a failure of non-surgical treatment in emphysematous pyelonephritis: A case report.

Emphysematous pyelonephritis (EP) is an uncommon condition involving acute severe necrotising infection in the renal parenchyma, perinephric space and collecting system, with a mortality rate of up to 13%. A 62-year-old male with poorly controlled diabetes mellitus presented with severe epigastric pain and shortness of breath for three days. A computed tomography scan revealed class 3B EP, which failed medical therapy and percutaneous drainage.