[
Worm,
2014]
Animal development is driven by robust, cell-specific gene expression programs. Understanding mechanistically how a single transcription factor (TF) can govern distinct programs with exquisite precision is a major challenge. We view TFs as signal integrators, taking information from co-regulator interactions, post-translational modifications, other transcription factors, chromatin state, DNA sequence and in some cases, specific noncovalent ligands, to determine the collection of genes regulated by a TF at any given time. Here, we describe a reductionist approach to combinatorial transcriptional regulation, focusing on a single C. elegans TF, the nuclear hormone receptor NHR-25, and a single post-translational modification, SUMO. We suggest that the ratio of sumoylated to unsumoylated NHR-25 could specify a switch-like cell-fate decision during vulval development. Direct examination of this "SUMO ratio" in vivo is challenging and we discuss possible solutions going forward. We also consider how sumoylation of multiple substrates might be coordinated during vulval development. Finally, we note that iteration of this approach could leverage our sumoylation findings to define the roles of other effectors of NHR-25 in the developing vulva and in other tissues.
[
Epigenet Insights,
2019]
It is now clear that heredity is not determined purely by Mendelian genetic inheritance; sometimes, epigenetic signals can be passed from parent to progeny for multiple generations. This phenomenon is termed transgenerational epigenetic inheritance (TEI), and examples have now been observed in multiple organisms including plants, flies, mice, and nematodes. Here we discuss the recent findings that TEI is a multi-step process and that the putative chromatin modifiers SET-25 and SET-32 are important in the establishment but not maintenance of silencing.
[
Microb Cell,
2018]
Iron plays many critical roles in human biology, such as aiding the transport of oxygen and mediating redox reactions. Iron is essential for life, yet little is known about how iron is taken up into mitochondria to impact the labile iron pool. Iron deficiency is one of the most prevalent human nutrient-deficiency diseases in the world and is a major cause of anemia that affects >25% of the world's population, but unfortunately the current treatment (oral iron supplementation) is inefficient and has many side effects. A greater understanding of iron uptake, and discovery of molecules that aid in this process, may lead to more effective treatments for iron deficiency. In this study, we uncovered a unique and surprising role for an <i>Escherichia coli</i>-produced siderophore enterobactin (Ent) that facilitates iron uptake by the host, observed in both <i>C. elegans</i> and mammalian cells. Although siderophores are well-known Fe<sup>+3</sup> scavengers, this activity has previously been described to only benefit iron acquisition by bacteria, not the host. This unexpected function is dependent on the binding of Ent to the host's ATP synthase -subunit but is independent of other subunits of the ATP synthase. This finding marks a major shift regarding the role of this siderophore in the "iron tug-of-war" paradigm, which is often used to describe the fight between the bacteria and the host for this essential micronutrient. Instead, this study presents <i>E. coli</i> as a commensal "friend" that provides a molecule that supports the host's iron homeostasis. This work reveals a novel, beneficial role of a bacteria-generated molecule in aiding the host's iron homeostasis, and points to surprising new benefits from commensal bacteria.