Mechanisms of force-mediated regulation of transcription, chromatin remodeling and cell fate decisions

Tissue mechanics and cellular interactions influence every single cell in our bodies to drive morphogenesis. However, little is known about mechanisms by which cells sense physical forces and transduce them from the cytoskeleton to the nucleus to control gene expression and stem cell fate. We have identified a novel nuclear-mechanosensor complex, consisting of the nuclear membrane protein emerin (Emd), actin and non-muscle myosin IIA (NMIIA), that regulates transcription, chromatin remodeling and lineage commitment. Force-induced enrichment of Emd at the outer nuclear membrane leads to a compensation between H3K9me2,3 and H3K27me3 on constitutive heterochromatin. This strain-induced epigenetic switch is accompanied by the global rearrangement of chromatin. In parallel, forces promote local F-actin polymerization at the outer nuclear membrane, which limits the availability of nuclear G-actin. Subsequently, the reduction of nuclear G-actin results in attenuated global transcription and therefore increased H3K27me3 occupancy to reinforce gene silencing. Restoring nuclear actin levels in the presence of mechanical strain counteracts PRC2-mediated silencing of transcribed genes. This mechanosensory circuit is also observed in vivo. Depletion of NMIIA in mouse epidermis leads to decreased H3K27me3 levels and precocious lineage commitment, thus abrogating organ growth and patterning. Our results reveal how mechanical signals regulate nuclear architecture, chromatin organization and transcription to control cell fate decisions.

The role of FMT and FIS1A in mitochondrial morphology and salt stress in Arabidopsis thaliana

Salt stress is known to have severe effects on plant health and fecundity, and mitochondria are known to be an essential part of the plant salt stress response. Arabidopsis thaliana serves as an excellent model to study the effects of salt stress as well as mitochondrial morphology. Arabidopsis contains several homologues to known mitochondrial proteins, including the fission protein FIS1A, and FMT, a homologue of the CLU subfamily. We sought to examine the effects of salt stress on knockout lines of FIS1A and FMT, as well as a transgenic line overexpressing FMT (FMT-OE) in columella cells in the root cap of Arabidopsis. fmt mutants displayed defects in both root and leaf growth, as well as a delay in flowering time. These mutants also showed a pronounced increase in mitochondrial clustering and number. FMT-OE mutants displayed severe defects in germination, including a decrease in total germination, and an increase in the number of days to germination. fis1A mutants exhibited shorter roots and slightly shorter leaves, as well as a tendency towards random mitochondrial clustering in root cells. Salt stress was shown to affect various mitochondrial parameters, including an increase in mitochondrial number and clustering, as well as a decrease in mitochondrial area. These results reveal a previously unknown role for FMT in germination and flowering in Arabidopsis, as well as insight into the effects of salt stress on mitochondrial morphology. FMT, along with FIS1A, may also help to regulate mitochondrial number and clustering, as well as root and leaf growth, under both control and salt-stressed conditions. This has implications for both FMT and FIS1A in whole-plant morphology as well as the plant salt stress response.