Fasting shapes chromatin architecture through an mTOR/RNA Pol I axis.

Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom, yet how it impacts three-dimensional (3D) genome organization is unknown. Here we show that fasting induces an intestine-specific, reversible and large-scale spatial reorganization of chromatin in Caenorhabditis elegans.

Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development.

The development of functional neurons is a complex orchestration of multiple signaling pathways controlling cell proliferation and differentiation. Because the balance of antioxidants is important for neuronal survival and development, we hypothesized that ferroptosis must be suppressed to gain neurons. We find that removal of antioxidants diminishes neuronal development and laminar organization of cortical organoids, which is fully restored when ferroptosis is inhibited by ferrostatin-1 or when neuronal differentiation occurs in the presence of vitamin A.

The influencers' era: how the environment shapes chromatin in 3D.

Environment-epigenome interactions are emerging as contributors to disease risk and health outcomes. In fact, organisms outside of the laboratory are constantly exposed to environmental changes that can influence chromatin regulation at multiple levels, potentially impacting on genome function. In this review, we will summarize recent findings on how major external cues impact on 3D chromatin organization in different experimental systems.

An mTOR/RNA pol I axis shapes chromatin architecture in response to fasting.

Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown.

Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei.

The execution of developmental programs of gene expression requires an accurate partitioning of the genome into subnuclear compartments, with active euchromatin enriched centrally and silent heterochromatin at the nuclear periphery. The existence of degenerative diseases linked to lamin A mutations suggests that perinuclear binding of chromatin contributes to cell-type integrity. The methylation of lysine 9 of histone H3 (H3K9me) characterizes heterochromatin and mediates both transcriptional repression and chromatin anchoring at the inner nuclear membrane.

Spatial segregation of heterochromatin: Uncovering functionality in a multicellular organism.

Multiple layers of regulation are required to ensure appropriate patterns of gene expression for accurate cell differentiation. Interphase chromatin is non-randomly distributed within the nucleus, with highly compacted, transcriptionally silent heterochromatin enriched at the nuclear and nucleolar periphery. Whether this spatial organization serves a function in organismal physiology, rather than simply being a byproduct of chromatin metabolism, is a fundamental question.

Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos.

Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9 methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously uncharacterized C.

Chromatin states and nuclear organization in development--a view from the nuclear lamina.

The spatial distribution of chromatin domains in interphase nuclei changes dramatically during development in multicellular organisms. A crucial question is whether nuclear organization is a cause or a result of differentiation. Genetic perturbation of lamina-heterochromatin interactions is helping to reveal the cross-talk between chromatin states and nuclear organization.

HnRNP A1 controls a splicing regulatory circuit promoting mesenchymal-to-epithelial transition.

Epithelial-to-mesenchymal transition (EMT) is an embryonic program used by cancer cells to acquire invasive capabilities becoming metastatic. ΔRon, a constitutively active isoform of the Ron tyrosine kinase receptor, arises from skipping of Ron exon 11 and provided the first example of an alternative splicing variant causatively linked to the activation of tumor EMT. Splicing of exon 11 is controlled by two adjacent regulatory elements, a silencer and an enhancer of splicing located in exon 12.

A novel molecular mechanism in human genetic disease: a DNA repeat-derived lncRNA.

Two thirds of the human genome is composed of repetitive sequences. Despite their prevalence, DNA repeats are largely ignored. The vast majority of our genome is transcribed to produce non protein-coding RNAs.

A long ncRNA links copy number variation to a polycomb/trithorax epigenetic switch in FSHD muscular dystrophy.

Repetitive sequences account for more than 50% of the human genome. Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disease associated with reduction in the copy number of the D4Z4 repeat mapping to 4q35. By an unknown mechanism, D4Z4 deletion causes an epigenetic switch leading to de-repression of 4q35 genes.

The cell biology of disease: FSHD: copy number variations on the theme of muscular dystrophy.

In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35.