Drosophila female sterile (1) homeotic is a multifunctional transcriptional regulator that is modulated by Ras signaling

The Drosophila ( fs ( 1 ) h ) gene encodes small ( Fs(1)hS ) and large ( Fs ( 1 ) hL ) chromatin‐binding BET protein transcription factor isoforms. Zygotic mutations cause either lethality or female sterility, whereas maternal mutations cause segmental deletions and thoracic homeotic transformations. Here, we describe novel fs ( 1 ) h embryonic phenotypes: homeosis of the head in zygotic mutants and deletion of head and tail regions in maternal mutants, similar to those caused by dominant torso ( tor D ) alleles. tor activates transcription of tailless ( tll ) and h ü ckebein ( hkb ) by means of a canonical Ras pathway, through inactivation of Groucho (Gro), Capicua (Cic) and, possibly, Grainy‐head (Grh) repressors. Expression of both tailless and h ü ckebein are de‐repressed in fs ( 1 ) h maternal mutants, as in tor D , gro , grh , and cic mutant animals, indicating fs ( 1 ) h is also necessary for tll and hkb repression. These data link Ras signaling with modulation of a chromatin‐binding transcription factor, Fs(1)h, suggesting a novel mechanism by which Ras can modulate gene expression. Developmental Dynamics 237:554–564, 2008. © 2008 Wiley‐Liss, Inc.