Abstract
BackgroundHeterochromatin 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Heterochromatin protein 1 (HP1) family proteins have a well-characterized role in heterochromatin packaging and gene regulation
Some of the down-regulated genes are likely to be indirect targets, these results suggest that HPL-2 may play a significant role in gene activation, as reported for certain other HP1 family proteins in both Drosophila and mammalian cells [5,11,13,31,32]
C. elegans provides an optimal system to explore the roles of HP1 beyond centromeric heterochromatin because worm chromosomes are holocentric and lack the alpha satellite repeats that nucleate the binding of HP1 to centromeres in other species
Summary
Heterochromatin protein 1 (HP1) family proteins have a well-characterized role in heterochromatin packaging and gene regulation. In most organisms, including mammals, environmental and physiological signals are integrated to regulate metabolism, development and life span In eukaryotes, these processes are often associated with characteristic epigenetic changes brought about by the activity of chromatin-associated proteins and enzymes that influence the transition between chromatin states, thereby influencing transcriptional activity. Among the more universally conserved epigenetic factors are members of the Heterochromatin protein 1 (HP1) family These contribute directly to the formation of nuclear heterochromatic domains, including telomeres and centromeres, through an interaction with trimethylated lysine 9 of histone H3 (H3K9me3) [1,2]. Both H3K9 methylation and HP1 binding at pericentromeric regions play a crucial role in chromosome segregation during mitosis [3,4]. This involves interactions with other proteins or RNA components, and leads to either gene activation or repression depending on the chromatin context [5,6,7]
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