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

Abstract

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)

Antagonistic action of Bicoid and the repressor Capicua determines the spatial limits of Drosophila head gene expression domains

“…Thus, the anteriormost Bcd target genes are not dependent on Tor-mediated phosphorylation of Bcd. It is likely that Tor downregulates a set of partially redundant repressors at the termini, including Grainyhead, Trithorax-like (16), Tramtrack69 (45), and Female Sterile (1) Homeotic (46), gradually restricting their activities to the central region, which results in Tor-dependent relief of repression (16). The available evidence supports the argument that mirror image duplications that are caused by uniform expression of Bcd are the result of the spatial restriction of repressors by Tor activity as exemplified here for Cic.…”

tBRD-1 Selectively Controls Gene Activity in the Drosophila Testis and Interacts with Two New Members of the Bromodomain and Extra-Terminal (BET) Family

“…BET proteins associate with chromatin and with the basal transcriptional machinery to modulate chromatin structure and influence transcription in a sequence-independent manner [20], [21]. In mammals, BRD2 is involved in gene activation, e.g.…”

The Role of the Double Bromodomain-Containing BET Genes During Mammalian Spermatogenesis

“…Not surprisingly, bromodomains are found in proteins with diverse functions, including histone acetyltransferases ( Jacobson, Ladurner, King, & Tjian, 2000; Mishima et al, 2011; Ohshima, Suganuma, & Ikeda, 2001; Wang et al, 1997), histone methyltransferases (Gregory et al, 2007; Hess, 2004), histone kinases (Xiao et al, 2009), transcriptional coactivators (Denis, 2010; Ogryzko, Schiltz, Russanova, Howard, & Nakatani, 1996; Tamkun, 1995), transcriptional corepressors (Sankar et al, 2008; Tae et al, 2011; Zeng et al, 2008; Zhou & Grummt, 2005), ubiquitin ligases (Agricola, Randall, Gaarenstroom, Dupont, & Hill, 2011; Allton et al, 2009), sumo ligases (Liang et al, 2011), and chromatin remodelers (Liu, Mulholland, Fu, & Zhao, 2006; Racki et al, 2009; Thompson, 2009; Wilson & Roberts, 2011). The ~110 aa-long bromodomain motif folds into two loops, each containing two alpha helices, thereby creating a hydrophobic pocket between them that interacts with acetylated lysine (Florence & Faller, 2008; Owen et al, 2000). Bromodomains have been shown to bind to acetylated lysines both in histone tails (Jacobson et al, 2000; Jeanmougin, Wurtz, Le Douarin, Chambon, & Losson, 1997) and in nonhistone proteins (Barlev et al, 2001; Gamsjaeger et al, 2011).…”

“…Numerous mutant alleles of fs(1)h have been characterized at the molecular level, revealing modular functions for the fs(1)h protein. The first such mutations were temperature-sensitive mutant alleles; however, it is important to note that even at high nonpermissive temperatures, fs(1)h protein was present, albeit at low levels, suggesting that these mutations do not reflect complete loss of function (Florence & Faller, 2008; Gans et al, 1975, 1980). When females were shifted to high (26.5–29° C) temperatures, a reduced number of nonproductive eggs were laid such that the flies were considered to be infertile.…”

“…Loss of fs(1)h function resulted in alteration of Ultrabithorax ( Ubx ) and trithorax ( trx ) expression, which in turn caused late segmentation defects (Huang & Dawid, 1990). In a study in which a highly conserved aspartic acid residue in BD1 was mutated to valine, a different mutant phenotype was observed (Florence & Faller, 2008). These mutant flies were also sterile, but the maternal effects resulted in head and gut defects caused by loss of repression of tailless ( tll ) and hückebein ( hkb ) at the initiation of transcription during embryogenesis.…”