Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites.

Long interspersed element 1 (L1) retrotransposons are implicated in human disease and evolution. Their global activity is repressed by DNA methylation, but deciphering the regulation of individual copies has been challenging. Here, we combine short- and long-read sequencing to unveil L1 methylation heterogeneity across cell types, families, and individual loci and elucidate key principles involved.

E4F1 and ZNF148 are transcriptional activators of the -57A > C and wild-type promoter.

Point mutations within the promoter are the most recurrent somatic noncoding mutations identified across different cancer types, including glioblastoma, melanoma, hepatocellular carcinoma, and bladder cancer. They are most abundant at -146C > T and -124C > T, and rarer at -57A > C, with the latter originally described as a familial case, but subsequently shown also to occur somatically. All three mutations create de novo E26-specific (ETS) binding sites and result in activation of the gene, allowing cancer cells to achieve replicative immortality.

A genome-wide screen reveals new regulators of the 2-cell-like cell state.

In mammals, only the zygote and blastomeres of the early embryo are totipotent. This totipotency is mirrored in vitro by mouse '2-cell-like cells' (2CLCs), which appear at low frequency in cultures of embryonic stem cells (ESCs). Because totipotency is not completely understood, we carried out a genome-wide CRISPR knockout screen in mouse ESCs, searching for mutants that reactivate the expression of Dazl, a gene expressed in 2CLCs.

Contribution and limits of clinical specimens for the screening of intestinal multi-drug-resistant bacteria in view of laboratory automation.

The detection of multi-drug-resistant bacteria carriers constitutes a race against time for infection preventionists. Alongside standard analysis for diagnostic purposes and a rectal screening strategy, the authors tested a heavy-loaded selective method against 562 clinical specimens from 439 patients to detect extended-spectrum beta-lactamase-producing (ESBL) or carbapenemase-producing Enterobacteriaceae (CPE) and vancomycin-resistant enterococci (VRE). The approach identified five more specimens positive for ESBL-producing Enterobacteriaceae than standard analysis, and six out of nine known VRE/CPE carriers (three new CPE/VRE strains were also identified in this cohort).