Approaches to characterize chromatin subcompartment organization in the cell nucleus.

The mechanism of self-organization of chromatin subcompartments on the 0.1-1 μm scale and their impact on genome-associated activities has long been a key aspect of research on nuclear organization. Understanding the underlying structure-function relationship, however, remains challenging due to the complex hierarchical structure of chromatin and the polymorphic organization of subcompartments that assemble around it.

Transcription activation is enhanced by multivalent interactions independent of phase separation.

Transcription factors (TFs) consist of a DNA-binding domain and an activation domain (AD) that are frequently considered to be independent and exchangeable modules. However, recent studies report that the physicochemical properties of the AD can control TF assembly at chromatin by driving phase separation into transcriptional condensates. Here, we dissected transcription activation by comparing different synthetic TFs at a reporter gene array with real-time single-cell fluorescence microscopy.

PITX1 Is a Regulator of TERT Expression in Prostate Cancer with Prognostic Power.

The current risk stratification in prostate cancer (PCa) is frequently insufficient to adequately predict disease development and outcome. One hallmark of cancer is telomere maintenance. For telomere maintenance, PCa cells exclusively employ telomerase, making it essential for this cancer entity.

ALT-FISH quantifies alternative lengthening of telomeres activity by imaging of single-stranded repeats.

Alternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA.

Transcriptional Activation of Heterochromatin by Recruitment of dCas9 Activators.

The transition from silenced heterochromatin to a biologically active state and vice versa is a fundamental part of the implementation of cell type-specific gene expression programs. To reveal structure-function relationships and dissect the underlying mechanisms, experiments that ectopically induce transcription are highly informative. In particular, the approach to perturb chromatin states by recruiting fusions of the catalytically inactive dCas9 protein in a sequence-specific manner to a locus of interest has been used in numerous applications.

Data for the assessment of vulnerability and resilience in the field of environmental health in the north of France.

The integration of multidimensional data is necessary to improve the understanding of environmental and social inequalities in health. The challenge is to define a dataset that provides the most holistic description possible of the territory. This article presents a relevant dataset to characterize the territorial accumulation of health determinants in the second most densely populated region of metropolitan France (Hauts-de-France Region, in the north of France).

Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD.

The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated.

MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus.

Long-term memory formation is supported by functional and structural changes of neuronal networks, which rely on de novo gene transcription and protein synthesis. The modulation of the neuronal transcriptome in response to learning depends on transcriptional and post-transcriptional mechanisms. DNA methylation writers and readers regulate the activity-dependent genomic program required for memory consolidation.

Repetitive RNAs as Regulators of Chromatin-Associated Subcompartment Formation by Phase Separation.

Repetitive RNA (repRNA) sequences emerge as important regulators of the dynamic organization of genomic loci into membrane-less subcompartments with distinct nuclear functions. These domains include sites of active transcription like the nucleolus as well as (peri)centromeric and telomeric satellite repeats. Recent studies point to an important role of repRNAs in complex with proteins to promote a phase separation-driven formation of chromatin domains.

Mouse Heterochromatin Adopts Digital Compaction States without Showing Hallmarks of HP1-Driven Liquid-Liquid Phase Separation.

The formation of silenced and condensed heterochromatin foci involves enrichment of heterochromatin protein 1 (HP1). HP1 can bridge chromatin segments and form liquid droplets, but the biophysical principles underlying heterochromatin compartmentalization in the cell nucleus are elusive. Here, we assess mechanistically relevant features of pericentric heterochromatin compaction in mouse fibroblasts.

The long non-coding RNA LINC00152 is essential for cell cycle progression through mitosis in HeLa cells.

In recent years, long non-coding RNA (lncRNA) research has identified essential roles of these transcripts in virtually all physiological cellular processes including tumorigenesis, but their functions and molecular mechanisms are poorly understood. In this study, we performed a high-throughput siRNA screen targeting 638 lncRNAs deregulated in cancer entities to analyse their impact on cell division by using time-lapse microscopy. We identified 26 lncRNAs affecting cell morphology and cell cycle including LINC00152.

Validation of the AgraStrip® gluten G12 test kit.

Romer Labs , Inc. developed an immunochromatographic lateral flow assay for the qualitative detection of gluten in raw ingredients, processed foods, finished food products, and environmental surfaces, using the G12 antibody developed by Belén Morón. The G12 antibody targets a 33-mer peptide which is resistant to enzymatic digestion and heat denatiuration, as well as being the fragment of the gliadin protein.