While terminally differentiated cells execute gene expression programs optimized for their unique functional identities, they must also maintain the ability to globally modulate transcription in response to physiological or environmental signals. We have begun to study the regulation of a C. elegans linker histone protein, HIL-1, in order to identify molecular mechanisms that underlie the implementation and the reversibility of adaptive plasticity in differentiated cells. Previous studies in the lab established that, of the 7 H1 linker histone genes in C. elegans,
hil-1 is singularly upregulated in most somatic cells in response to dauer entry signals. Upon depletion of DAF-2/IGF signaling or under starved conditions,
hil-1 mRNA levels increase 40 fold and nuclear HIL-1 protein accumulation increases at least 100 fold [1]. Histone variant proteins in different organisms have previously been found to be upregulated under specific environmental or physiological scenarios, and the expression of H1 variants in multiple species often correlates with cell-type-specific differentiation [2, 3]. Moreover, H3 and H2A variants have been found to localize to specific chromatin domains [4, 5]. What are the molecular mechanisms that regulate the specific accumulation of variant histone proteins into chromatin? The dramatic induction of
hil-1 expression provides us with a unique genetic system to directly screen for factors that regulate widespread incorporation and maintenance of a replacement-type histone into chromatin of post-mitotic cells. Moreover, as HIL-1 induction is reversible, we can also use this system to screen for trans-acting molecules that regulate removal of HIL-1 protein from chromatin upon restoration of nutritional or DAF-2 signals. Our genetic approach uses an integrated DNA array which contains 1)
hil-1 5' promoter sequences driving expression of CFP 2) a HIL-1-YFP translational fusion protein which is driven by
hil-1 promoter sequences and 3) the
rol-6(+) gene. We will report our characterization of the kinetics of
hil-1 transcriptional and nuclear accumulation in response to nutritional and insulin signals in worms carrying this integrated array, and will present preliminary results of a screen designed to identify genes that regulate HIL-1 protein accumulation and removal, but are dispensable for
hil-1 transcription. 1.Jones, S.J., et al. Genome Res, 2001. 11(8): p. 1346-52. 2.Scippa, G.S., et al. Planta, 2000. 211(2): p. 173-81. 3.Zlatanova, J. and D. Doenecke, Faseb J, 1994. 8(15): p. 1260-8. 4.Ahmad, K. and S. Henikoff, Mol Cell, 2002. 9(6): p. 1191-200. 5.Redon, C., et al.. Curr Opin Genet Dev, 2002. 12(2): p. 162-9.