CDCA7-associated global aberrant DNA hypomethylation translates to localized, tissue-specific transcriptional responses.

Disruption of cell division cycle associated 7 (CDCA7) has been linked to aberrant DNA hypomethylation, but the impact of DNA methylation loss on transcription has not been investigated. Here, we show that CDCA7 is critical for maintaining global DNA methylation levels across multiple tissues in vivo. A pathogenic missense variant leads to the formation of large, aberrantly hypomethylated domains overlapping with the B genomic compartment but without affecting the deposition of H3K9 trimethylation (H3K9me3).

Sub-micrometer four-point probe transport measurements on graphene.

Usually, electronic transport measurements on two-dimensional materials, such as graphene and transition metal dichalcogenides, require deposition of electrodes on top of the material, in, for instance, the form of a Hall bar device. In this work, we show that by making use of a collinear micro-four-point probe, electrical transport measurements on small flakes of graphene can be performed without having to fabricate electrodes on top of the flakes. Using probes with probe pitches down to sub-micrometer scale, we show back-gate tuned transport measurements in graphene on silicon oxide and on hexagonal boron nitride.

Depolymerization of supramolecular polymers by a covalent reaction; transforming an intercalator into a sequestrator.

Controlling the reciprocity between chemical reactivity and supramolecular structure is a topic of great interest in the emergence of molecular complexity. In this work, we investigate the effect of a covalent reaction as a trigger to depolymerize a supramolecular assembly. We focus on the impact of an thiol-ene reaction on the (co)polymerization of three derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with cysteine, hexylcysteine, and alkyl side chains: , , and .

The role of MORC3 in silencing transposable elements in mouse embryonic stem cells.

Background: Microrchidia proteins (MORCs) are involved in epigenetic gene silencing in a variety of eukaryotic organisms. Deletion of MORCs result in several developmental abnormalities and their dysregulation has been implicated in developmental disease and multiple cancers. Specifically, mammalian MORC3 mutations are associated with immune system defects and human cancers such as bladder, uterine, stomach, lung, and diffuse large B cell lymphomas.

Consequences of Molecular Architecture on the Supramolecular Assembly of Discrete Block Co-oligomers.

Supramolecular block copolymers composed of discrete blocks have promising properties for nanotechnology resulting from their ability to combine well-defined morphologies with good bulk material properties. Here, we present the impact of a well-defined siloxane block in either the main-chain or present as pendant grafts on the properties of supramolecular block copolymers that form ordered nanostructures with sub-5 nm domains. For this, two types of supramolecular block copolymers were synthesized based on the ureidopyrimidinone-urethane (UPy-UT) motif.

Synthesis and Self-Assembly of AB Miktoarm Star Polymers.

The stability of tetrahedrally close-packed (TCP) phases in block copolymer melts is predicted by theory to depend on molecular architecture, yet no experimental studies to date have probed its effect. Motivated by this open question, here we report an efficient synthesis of asymmetric AB miktoarm star polymers using functionalized sugars as cores for orthogonal grafting-from block copolymerizations. A combination of ring-opening and atom transfer radical polymerization produced model low dispersity materials comprising a single A = poly(lactide) (L) and multiple B = poly(dodecyl acrylate) (D) arms that amplify "conformational asymmetry" through two concerted effects: the mikto architecture and disparate block statistical segment lengths.

A functional assay to classify ZBTB24 missense variants of unknown significance.

Increasing use of next-generation sequencing technologies in clinical diagnostics allows large-scale discovery of genetic variants, but also results in frequent identification of variants of unknown significance (VUSs). Their classification into disease-causing and neutral variants is often hampered by the absence of robust functional tests. Here, we demonstrate that a luciferase reporter assay, in combination with ChIP-qPCR, reliably separates pathogenic ZBTB24 missense variants in the context of immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome from natural variants in healthy individuals and patients of other diseases.

The prebiotic inulin modulates gut microbiota but does not ameliorate atherosclerosis in hypercholesterolemic APOE*3-Leiden.CETP mice.

Gut microbiota have been implicated in the development of atherosclerosis and cardiovascular disease. Since the prebiotic inulin is thought to beneficially affect gut microbiota, we aimed to determine the effect of inulin supplementation on atherosclerosis development in APOE*3-Leiden.CETP (E3L.

A Restricted Role for FcγR in the Regulation of Adaptive Immunity.

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design.

Converging disease genes in ICF syndrome: ZBTB24 controls expression of CDCA7 in mammals.

For genetically heterogeneous diseases a better understanding of how the underlying gene defects are functionally interconnected will be important for dissecting disease etiology. The Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome is a chromatin disorder characterized by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS Here, we generated a Zbtb24 BTB domain deletion mouse and found that loss of functional Zbtb24 leads to early embryonic lethality. Transcriptome analysis identified Cdca7 as the top down-regulated gene in Zbtb24 homozygous mutant mESCs, which can be restored by ectopic ZBTB24 expression.

Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype.

The number of reports of paternal epigenetic influences on the phenotype of offspring in rodents is increasing but the molecular events involved remain unclear. Here, we show that haploinsufficiency for the histone 3 lysine 9 methyltransferase Setdb1 in the sire can influence the coat colour phenotype of wild type offspring. This effect occurs when the allele that directly drives coat colour is inherited from the dam, inferring that the effect involves an "in trans" step.