Directed Growth of Biomimetic Microcompartments.

Contemporary biological cells are sophisticated and highly compartmentalized. Compartmentalization is an essential principle of prebiotic life as well as a key feature in bottom-up synthetic biology research. In this review, the dynamic growth of compartments as an essential prerequisite for enabling self-reproduction as a fundamental life process is discussed. The micrometer-sized compartments are focused on due to their cellular dimensions. Two types of compartments are considered, membraneless droplets and membrane-bound microcompartments. Growth mechanisms of aqueous droplets such as protein (condensates) or macromolecule-rich droplets (aqueous two phase systems) and coacervates are discussed, for which growth occurs via Ostwald ripening or coalescence. For membrane-bound compartments, vesicles are considered, which are composed of fatty acids, lipids, or polymers, where directed growth can occur via fusion or uptake of material from the surrounding. The development of novel approaches for growth of biomimetic microcompartments can eventually be utilized to construct new synthetic cells.

Transgenerational transmission of environmental information in C. elegans.

The environment experienced by an animal can sometimes influence gene expression for one or a few subsequent generations. Here, we report the observation that a temperature-induced change in expression from a Caenorhabditis elegans heterochromatic gene array can endure for at least 14 generations. Inheritance is primarily in cis with the locus, occurs through both oocytes and sperm, and is associated with altered trimethylation of histone H3 lysine 9 (H3K9me3) before the onset of zygotic transcription. Expression profiling reveals that temperature-induced expression from endogenous repressed repeats can also be inherited for multiple generations. Long-lasting epigenetic memory of environmental change is therefore possible in this animal.

Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory.

Impaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as a cause of increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an "epiallele," being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states.

Mechanisms, timescales and principles of trans-generational epigenetic inheritance in animals.

Development never starts from a blank slate of DNA. Therefore, in principle, plenty beyond DNA could transmit phenotypic information from one generation to the next. However, the extent to which epigenetic information is actually transmitted between generations and whether this information is modulated by the environment are questions that have only recently started to be investigated at the molecular level. Here we review molecular work on inter-generation epigenetic effects in animals and highlight some principles of epigenetic transmission. We argue that the need to stably repress repetitive DNA facilitated the evolution of mechanisms conferring long-term epigenetic memory, that individual effectors such as small RNAs can provide short-term epigenetic memory, and that feedback between different epigenetic mechanisms - for example between chromatin and small RNAs - could contribute to more stable long-term inheritance. Environmentally-triggered epigenetic 'wounds' in heterochromatin that take one or more generations to 'heal' may also represent quite a generic mechanism for the transmission of acquired traits. Whether and how somatic cells alter epigenetic information in the germline, and whether and how long-term epigenetic memory can be transmitted without establishing permanent epigenetic states are key questions for future research.

Probing the interactions of carboxy-atractyloside and atractyloside with the yeast mitochondrial ADP/ATP carrier.

Mitochondrial ADP/ATP carriers are inhibited by two natural compounds, atractyloside (ATR) or carboxy-atractyloside (CATR), which differ by one carboxylate group. The interactions of the inhibitors with the carrier were investigated by single-molecule force spectroscopy. Transmembrane alpha helices of the ATR-inhibited carrier displayed heterogeneous mechanical and kinetic properties. Whereas alpha helix H2 showed the most brittle mechanical properties and lowest kinetic stability, alpha helix H5 was mechanically the most flexible and possessed a kinetic stability 9 orders of magnitude greater than that of alpha helix H2. In contrast, CATR-binding substantially increased the kinetic stability of alpha helix H2 and tuned the mechanical flexibility of alpha helices H5 and H6. NMR spectroscopy confirmed that the additional carboxylate group of CATR binds to the sixth alpha helix, indicating that the enhanced stability of H2 is mediated via interactions between CATR and H6.