Two distinct domains of Bicoid mediate its transcriptional downregulation by the Torso pathway

Abstract

The transcriptional activity of the Bicoid morphogen is directly downregulated by the Torso signal transduction cascade at the anterior pole of the Drosophila embryo. This regulation does not involve the homeodomain or direct phosphorylation of Bicoid. We analyse the transcriptional regulation of Bicoid in response to the Torso pathway, using Bicoid variants and fusion proteins between the Bicoid domains and the Gal4 DNA-binding domain. We show that Bicoid possesses three autonomous activation domains. Two of these domains, the serine/threonine-rich and the acidic domains, are downregulated by Torso, whereas the third activation domain, which is rich in glutamine, is not. The alanine-rich domain, previously described as an activation domain in vitro, has a repressive activity that is independent of Torso. Thus, Bicoid downregulation by Torso results from a competition between the glutamine-rich domain that is insensitive to Torso and the serine/threonine-rich and acidic activation domains downregulated by Torso. The alanine-rich domain contributes to this process indirectly by reducing the global activity of the protein and in particular the activity of the glutamine-rich domain that might otherwise prevent downregulation by Torso.

Shaping the scaling characteristics of gap gene expression patterns in Drosophila

“…The earliest patterns in Drosophila embryos are formed by the expression domains of gap genes in respond to the Bcd gradient [ [13] , [14] , [15] , [16] , [17] ]. It is well documented that, in addition to the Bcd input, the terminal system also plays important roles in driving gap gene expression [ [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] ]. Furthermore, it is actively debated whether the Bcd input exerts a sustained control over the AP patterning network during development [ 21 , [24] , [25] , [26] , [27] ].…”

SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence

“…10/11 subunits of the SWI/SNF complex contain large intrinsically disordered regions ( Figure 1—figure supplement 1 ), and in particular, 4/11 SWI/SNF subunits contain glutamine-rich low-complexity sequences (QLCs). QLCs are present in glutamine-rich transactivation domains ( Kadonaga et al, 1988 ; Kadonaga et al, 1987 ) some of which, including those found within SWI/SNF, may bind to transcription factors ( Prochasson et al, 2003 ) or recruit transcriptional machinery ( Geng et al, 2001 ; Janody et al, 2001 ; Laurent et al, 1990 ). Intrinsically disordered regions lack a fixed three-dimensional structure and can be highly responsive to their solution environment ( Holehouse and Sukenik, 2020 ; Moses et al, 2020 ).…”

Cooption of polyalanine tract into a repressor domain in the mammalian transcription factor HoxA11

“…For example, how have transcription factors evolved and modularized their regulatory functions, how are these functions maintained despite sequence divergence, and how do functional changes occur without strong negative pleiotropic effects? Simple sequence repeats, such as long tracts of the same amino acid (homopolymers), are common in eukaryotic transcription factors, particularly developmental genes (Karlin and Burge, 1996;Briata et al, 1997;Albà et al, 1999;Young et al, 2000;Janody et al, 2001;Albà and Guigo, 2004;Faux et al, 2005). These regions are extremely variable between species (Briata et al, 1997;Albà et al, 1999;Albà and Guigo, 2004) and have been associated with morphological evolution (Galant and Carroll, 2002;Ronshaugen et al, 2002;Fondon and Garner, 2004;Anan et al, 2007), suggesting they contribute to the functional diversity of transcriptional regulators (King et al, 1997;Kashi and King, 2006;Lynch and Wagner, 2008).…”

“…Polyalanine tracts, for example, account for ~17% of all human homopolymeric protein sequences (Karlin et al, 2002) and expansions of polyalanine tracts in at least 11 genes have been associated with developmental defects and diseases (Brown & Brown, 2004). Despite their ubiquity and association with diseases, however, few functions have been identified for amino acid repeats (Emili et al, 1994; Galant & Carroll, 2002; Gerber et al, 1994; Janody et al, 2001; Salichs et al, 2009; Xiao & Jeang, 1998).…”

“…associated with developmental defects and diseases (Brown & Brown, 2004). Despite their ubiquity and association with diseases, however, few functions have been identified for amino acid repeats (Emili et al, 1994;Galant & Carroll, 2002;Gerber et al, 1994;Janody et al, 2001;Salichs et al, 2009;Xiao & Jeang, 1998).…”