H3K27 demethylases, at long last

Methylation of lysine 27 on histone H3 (H3K27me) by the Polycomb complex (PRC2) proteins is associated with gene silencing in many developmental processes. A cluster of recent papers (Agger et al., 2007; De Santa et al., 2007; Lan et al., 2007; Lee et al., 2007) identify the JmjC-domain proteins UTX and JMJD3 as H3K27-specific demethylases that remove this methyl mark, enabling the activation of genes involved in animal body patterning and the inflammatory response.     

Bone remodeling, energy metabolism, and the molecular clock

The adult skeleton is constantly renewed through bone remodeling. Four recent papers (Baldock et al., 2007; Lee et al., 2007; Lundberg et al., 2007; Sato et al., 2007) provide new insights into central and peripheral control of this remodeling sequence. Two of the studies add to our knowledge of the complex hypothalamic modulation of bone turnover mediated by NMU and NPY via the sympathetic nervous system, while the other two focus on the peripheral neural target, the osteoblast, and its regulation by neuropeptides and osteocalcin. These findings support a new paradigm concerning the regulation of bone remodeling and provide a foundation for novel approaches to preventing osteoporosis.     

Mighty Piwis defend the germline against genome intruders

Piwis are a germline-specific subclass of the Argonaute family of RNA interference (RNAi) effector proteins that are associated with a recently discovered group of small RNAs (piRNAs). Recent studies in Drosophila and zebrafish directly implicate Piwi proteins in piRNA biogenesis to maintain transposon silencing in the germline genome (Brennecke et al., 2007; Gunawardane et al., 2007; Houwing et al., 2007). This function may be conserved in mice as loss of Miwi2, a mouse Piwi homolog, leads to germline stem cell and meiotic defects correlated with increased transposon activity (Carmell et al., 2007).     

Centromere Epigenetics in Plants

The centromere is an essential chromosome site at which the kinetochore forms and loads proteins needed for faithful segregation during the cell cycle and meiosis(Houben et al., 1999;Cleveland et al.,2003;Ma et al.,2007;Birchler and Han,2009).Centromere specific sequences such as tandem repeats or transposable elements evolve quickly both within and between the species but have conserved kinetochore proteins(Henikoff and Furuyama,2010).The universal feature     

After hours keeps clock researchers CRYing Overtime

Three recent reports, including one in this issue of Cell, reveal that the circadian regulator CRY is targeted for degradation by the F box E3 ubiquitin ligase FBXL3 (Siepka et al., 2007; Busino et al., 2007; Godinho et al., 2007). These studies confirm the importance of targeted protein degradation as a key design feature of the mammalian circadian clock.     

A backup DNA repair pathway moves to the forefront

Chromosomal translocations between antigen receptor loci and oncogenes are a hallmark of lymphoid cancers. Several new studies now reveal that programmed DNA breaks created during assembly of antigen receptor genes can be channeled into an alternative DNA end-joining pathway that is implicated in the chromosomal translocations of lymphoid cancers (Corneo et al., 2007; Soulas-Sprauel et al., 2007; Yan et al., 2007).     

A quorum on bacterial programmed cell death

A recent article in Science (Kolodkin-Gal et al., 2007) reported a novel programmed cell death mechanism for Escherichia coli that occurs during cellular overcrowding via the release of a fratricidal pentapeptide derived from the metabolic enzyme glucose-6-phosphate dehydrogenase.     

Dscam and neuronal uniqueness

In the fruit fly Drosophila the gene encoding the cell adhesion molecule Dscam generates alternatively spliced mRNAs that can be translated into thousands of different protein isoforms. Three recent papers show that isoform-specific homophilic Dscam interactions cause dendritic branches of the same neuron to avoid each other (Hughes et al., 2007; Soba et al., 2007; Matthews et al., 2007). This process ensures the correct patterning of dendrites in the peripheral nervous system.     

Epigenetic Variations in Plant Hybrids and Their Potential Roles in Heterosis

Heterosis,one of the most important biological phenomena,refers to the phenotypic superiority of a hybrid over its genetically diverse parents with respect to many traits such as biomass,growth rate and yield.Despite its successful application in breeding and agronomic production of many crop and animal varieties,the molecular basis of heterosis remains elusive.The classic genetic explanations for heterosis centered on three hypotheses:dominance (Davenport,1908;Bruce,1910;Keeble and Pellew,1910;Jones,1917),overdominance (East,1908;Shull,1908) and epistasis (Powers,1944;Yu et al.,1997).However,these hypotheses are largely conceptual and not connected to molecular principles,and are therefore insufficient to explain the molecular basis of heterosis (Birchler et al.,2003).Recently,many studies have explored the molecular mechanism of heterosis in plants at a genome-wide level.These studies suggest that global differential gene expression between hybrids and parental lines potentially contributes to heterosis in plants (e.g.,Swanson-Wagner et al.,2006;Zhang et al.,2008;Wei et al.,2009;Song et al.,2010).Research suggests that genetic components,including cis-acting elements and trans-acting factors,are critical regulators of differential gene expression in hybrids (Hochholdinger and Hoecker,2007;Springer and Stupar,2007;Zhang et al.,2008).However,other research indicates that epigenetic components,the regulators of chromatin states and genome activity,also have the potential to impact heterosis (e.g.,Ha et al.,2009;He et al.,2010;Groszmann et al.,2011;Barber et al.,2012;Chodavarapu et al.,2012;Greaves et al.,2012a;Shen et al.,2012).     

A two-way street: LSD1 regulates chromatin boundary formation in S. pombe and Drosophila

Two recent studies in Molecular Cell (Lan et al., 2007; Rudolph et al., 2007) implicate histone demethylation by LSD1 in the regulation of boundaries between silenced and active chromatin domains in both fission yeast and flies, but by distinct mechanisms.     

Smac mimetics and TNFalpha: a dangerous liaison?

Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death.     

Inositol pyrophosphate pyrotechnics

Physiologic roles of highly phosphorylated inositol phosphates, including those containing pyrophosphate groups, have been the focus of much recent interest. In the April 6, 2007 issue of Science, two papers (Lee et al., 2007; Mulugu et al., 2007) demonstrate the occurrence of a novel inositol pyrophosphate molecule in yeast and elucidate its role in phosphate homeostasis.     

Does FASing out new fat in the hypothalamus make you slim?

Fatty acid synthase (FAS) is a key enzyme for lipogenesis. A recent study (Chakravarthy et al., 2007) shows that the targeted deletion of FAS in hypothalamic neurons produces hypophagic, lean mice and suggests that PPARalpha signaling is an important mediator of the effects of FAS on energy homeostasis.     

Multiple Forms and Distribution of Calcium/Calmodulin-Stimulated Protein Kinase II in Brain

In recent years, the enzyme Ca²⁺/calmodulin-stimulated protein kinase II¹ (CaM-PK II) as attracted a great deal of interest. CaM-PK II is the most abundant calmodulin-stimulated protein kinase in brain, where it is particularly enriched in neurons (Ouimet et al., 1984; Erondu and Kennedy, 1985; Lin et al., 1987; Scholz et al., 1988). Neuronal CaM-PK II has been suggested to be involved in several phenomena associated with synaptic plasticity (Lisman and Goldring, 1988; Kelly, 1992), including long-term potentiation (Malinow et al., 1988; Malenka et al.,1989), neurotransmission (Nichols et al., 1990; Siekevitz, 1991), and learning (for review, see Rostas, 1991). This enzyme has also been postulated to be selectively vulnerable in several pathological condition, including epilepsy/kindling (Bronstein et al.,1990; Wu et al., 1990), cerebral ischemia (Taft et al., 1988), and organophosphorus toxicity (Abou-Donia and Lapadula, 1990).     

Reply to response to Dyck et al. (2007) on polar bears and climate change in western Hudson Bay by Stirling et al. (2008)

We address the three main issues raised by Stirling et al. [Stirling, I., Derocher, A.E., Gough, W.A., Rode, K., in press. Response to Dyck et al. (2007) on polar bears and climate change in western Hudson Bay. Ecol. Complexity]: (1) evidence of the role of climate warming in affecting the western Hudson Bay polar bear population, (2) responses to suggested importance of human–polar bear interactions, and (3) limitations on polar bear adaptation to projected climate change. We assert that our original paper did not provide any “alternative explanations [that] are largely unsupported by the data” or misrepresent the original claims by Stirling et al. [Stirling, I., Lunn, N.J., Iacozza, I., 1999. Long-term trends in the population ecology of polar bears in western Hudson Bay in relation to climate change. Arctic 52, 294–306], Derocher et al. [Derocher, A.E., Lunn, N.J., Stirling, I., 2004. Polar bears in a warming climate. Integr. Comp. Biol. 44, 163–176], and other peer-approved papers authored by Stirling and colleagues. In sharp contrast, we show that the conclusion of Stirling et al. [Stirling, I., Derocher, A.E., Gough, W.A., Rode, K., in press. Response to Dyck et al. (2007) on polar bears and climate change in western Hudson Bay. Ecol. Complexity] – suggesting warming temperatures (and other related climatic changes) are the predominant determinant of polar bear population status, not only in western Hudson (WH) Bay but also for populations elsewhere in the Arctic – is unsupportable by the current scientific evidence.The commentary by Stirling et al. [Stirling, I., Derocher, A.E., Gough, W.A., Rode, K., in press. Response to Dyck et al. (2007) on polar bears and climate change in western Hudson Bay. Ecol. Complexity] is an example of uni-dimensional, or reductionist thinking, which is not useful when assessing effects of climate change on complex ecosystems. Polar bears of WH are exposed to a multitude of environmental perturbations including human interference and factors (e.g., unknown seal population size, possible competition with polar bears from other populations) such that isolation of any single variable as the certain root cause (i.e., climate change in the form of warming spring air temperatures), without recognizing confounding interactions, is imprudent, unjustified and of questionable scientific utility. Dyck et al. [Dyck, M.G., Soon, W., Baydack, R.K., Legates, D.R., Baliunas, S., Ball, T.F., Hancock, L.O., 2007. Polar bears of western Hudson Bay and climate change: Are warming spring air temperatures the “ultimate” survival control factor? Ecol. Complexity, 4, 73–84. doi:10.1016/j.ecocom.2007.03.002] agree that some polar bear populations may be negatively impacted by future environmental changes; but an oversimplification of the complex ecosystem interactions (of which humans are a part) may not be beneficial in studying external effects on polar bears. Science evolves through questioning and proposing hypotheses that can be critically tested, in the absence of which, as Krebs and Borteaux [Krebs, C.J., Berteaux, D., 2006. Problems and pitfalls in relating climate variability to population dynamics. Clim. Res. 32, 143–149] observe, “we will be little more than storytellers.”     

miRNAs play a tune

Two new studies describe functionally relevant interactions between microRNAs (miRNAs) and their targets in the immune system and the brain (Xiao et al., 2007; Karres et al., 2007). Furthermore, these studies illustrate the involvement of miRNAs in tuning the expression of target genes to physiologically relevant levels.     

BDNF instructs the kinase LKB1 to grow an axon

Determining which neurite of a differentiating neuron is to become the axon is a crucial step in neuronal morphogenesis. Two groups (Barnes et al., 2007; Shelly et al., 2007) now report that axon specification in vivo is mediated by extracellular signals acting through the serine/threonine kinase LKB1.     

Making the right moves

The structure of the nucleotide-free F(1)-ATPase from a thermoalkaliphilic bacterium presented in this issue of Structure (Stocker et al., 2007) reveals the structural interactions that prevent the enzyme from operating naturally in the hydrolytic direction. The data provide new insights into the mechanism of the F(o)F(1)-ATP synthase.