A conserved function of the chromatin ATPase Kismet in the regulation of hedgehog expression

Abstract

The development of the Drosophila melanogaster wing depends on its subdivision into anterior and posterior compartments, which constitute two independent cell lineages since their origin in the embryonic ectoderm. The anterior-posterior compartment boundary is the place where signaling by the Hedgehog pathway takes place, and this requires pathway activation in anterior cells by ligand expressed exclusively in posterior cells. Several mechanisms ensure the confinement of hedgehog expression to posterior cells, including repression by Cubitus interruptus, the co-repressor Groucho and Master of thick veins. In this work we identified Kismet, a chromodomain-containing protein of the SNF2-like family of ATPases, as a novel component of the hedgehog transcriptional repression mechanism in anterior compartment cells. In kismet mutants, hedgehog is ectopically expressed in a domain of anterior cells close to the anterior-posterior compartment boundary, causing inappropriate activation of the pathway and changes in the development of the central region of the wing. The contribution of Kismet to the silencing of hedgehog expression is limited to anterior cells with low levels of the repressor form of Cubitus interruptus. We also show that knockdown of CHD8, the kismet homolog in Xenopus tropicalis, is also associated with ectopic sonic hedgehog expression and up-regulation of one of its target genes in the eye, Pax2, indicating the evolutionary conservation of Kismet/CHD8 function in negatively controlling hedgehog expression.

Misexpression screen delineates novel genes controlling Drosophila lifespan

“…Reduced expression of Drosophila kis yields similar pathogenic phenotypes including defects in motor ability, neuronal development, and learning/memory (Melicharek et al, 2010). Kismet also functions in circadian photo-response and control of hedgehog expression (Dubruille et al, 2009; Terriente-Felix et al, 2011). Over-expression of Kismet may increase longevity by increasing chromatin silencing and homeostasis (Oberdoerffer and Sinclair, 2007).…”

Chd8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling

“…Drosophila ortholog of Chd8, Kismet, regulates hedgehog (hh) expression in the wing imaginal disc in a context when expression of the repressor, Ci-75, is low 50 . However, Kismet is not necessary for the regulation of hh expression when Ci-75 expression is high, suggesting a context-dependent function 50 . A similar context-dependent mechanism could account for differences in regulation of Wnt signaling by Chd8.…”

Reversible switching between epigenetic states in honeybee behavioral subcastes

“…This subset of epigenetically reversible genes showed enrichment for development, ATP binding and nuclear pore formation (Supplementary Table 2). These genes include the ortholog to kismet, LOC726524, which regulates developmental genes such as hedgehog and affect learning and axon migration in Drosophila 12,13 , and might explain observed differences in learning 14 between nurses and foragers. In addition, DEAD-box helicase genes LOC725306 15 and LOC726524 both have roles in transcription, whereas LOC411989 is involved in translation 16 .…”