Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism

Background Heterochromatin protein 1 (HP1) family proteins have a well-characterized role in heterochromatin packaging and gene regulation. Their function in organismal development, however, is less well understood. Here we used genome-wide expression profiling to assess novel functions of the Caenorhabditis elegans HP1 homolog HPL-2 at specific developmental stages. Results We show that HPL-2 regulates the expression of germline genes, extracellular matrix components and genes involved in lipid metabolism. Comparison of our expression data with HPL-2 ChIP-on-chip profiles reveals that a significant number of genes up- and down-regulated in the absence of HPL-2 are bound by HPL-2. Germline genes are specifically up-regulated in hpl-2 mutants, consistent with the function of HPL-2 as a repressor of ectopic germ cell fate. In addition, microarray results and phenotypic analysis suggest that HPL-2 regulates the dauer developmental decision, a striking example of phenotypic plasticity in which environmental conditions determine developmental fate. HPL-2 acts in dauer at least partly through modulation of daf-2/IIS and TGF-β signaling pathways, major determinants of the dauer program. hpl-2 mutants also show increased longevity and altered lipid metabolism, hallmarks of the long-lived, stress resistant dauers. Conclusions Our results suggest that the worm HP1 homologue HPL-2 may coordinately regulate dauer diapause, longevity and lipid metabolism, three processes dependent on developmental input and environmental conditions. Our findings are of general interest as a paradigm of how chromatin factors can both stabilize development by buffering environmental variation, and guide the organism through remodeling events that require plasticity of cell fate regulation.

Weak Senses as a Type of Semantic Information

'Weak senses' are a specific type of semantic information as opposed to assertions and presuppositions. The universal trait of weak senses is that they assume 'if' modality in negative contexts. In addition they exhibit several other diagnostic properties, e.g. they fill at least one of their valency places with a semantic element sensitive to negation (i.e. with an assertion or other weak sense), they normally do not fall within the scope of functors, do not play any role in causal relations, and resist intensification. As weak senses are widespread in lexical, grammatical and referential semantics, this notion holds the clue to phenomena as diverse as the oppositions little - a little, few - a few, edva ('hardly') - cut' ('slightly), where a little, a few, cut, convey 'weakly' approximately what little, few, and edva do in an assertive way, the semantics of the Russian perfect aspect, and the formation rules for conjunction strings. Zeldovich outlines a typology of weak senses, the main distinction being between weak senses unilaterally dependent upon the truthfulness of what they saturate their valency with, and weak senses exerting their own influence on the main situation. The latter, called, non-trivial, are instantiated by existential quantifiers involved in the semantics of indefinite pronouns, iterative verbs, etc.