PWWP-mutants of the transcriptional cofactor JASPer divert promoter and enhancer activities and suppress position effect variegation in Drosophila

Through a new Su(var) screen, we identified Su140 and Su113 as very strong Su(var) mutants that are epistatic over Su(var)3-9 in the In(1)wm4h PEV rearrangement. Both Su140 and Su113 encode point mutations in the PWWP domain of the transcriptional cofactor JASPer that has described functions in protecting gene activity in euchromatin.

In JasperSu140/Su140 and JasperSu113/Su113 nuclear cycle (NC14) mutant embryos, heterochromatic marks (H3K9me2 and H3K9me3) are reduced, while activating histone modifications (H3K4me1 and H3K27ac) become enriched at heterochromatin. Whereas wild-type JASPer is enriched over H3K36me3-positive regions in gene bodies, JASPerSu140 is redistributed to regulatory elements in promoters and enhancers. JASPerSu140 directly binds and activates the white gene enhancer in NC14 embryos and JasperSu140/Su140 mutants induce a partial decompaction of the heterochromatin compartment containing the In(1)wm4h rearrangement.