Differential Occupancy of Two GA-Binding Proteins Promotes Targeting of the Drosophila Dosage Compensation Complex to the Male X Chromosome

Abstract

Summary: Little is known about how variation in sequence composition alters transcription factor occupancy to precisely recruit large transcription complexes. A key model for understanding how transcription complexes are targeted is the Drosophila dosage compensation system in which the male-specific lethal (MSL) transcription complex specifically identifies and regulates the male X chromosome. The chromatin-linked adaptor for MSL proteins (CLAMP) zinc-finger protein targets MSL to the X chromosome but also binds to GA-rich sequence elements throughout the genome. Furthermore, the GAGA-associated factor (GAF) transcription factor also recognizes GA-rich sequences but does not associate with the MSL complex. Here, we demonstrate that MSL complex recruitment sites are optimal CLAMP targets. Specificity for CLAMP binding versus GAF binding is driven by variability in sequence composition within similar GA-rich motifs. Therefore, variation within seemingly similar cis elements drives the context-specific targeting of a large transcription complex. : Kaye et al. investigate two transcription factors, GAF and CLAMP, that target similar GA-rich sequences yet have distinct occupancy. They identify specific features that distinguish binding of each factor and reveal that CLAMP and GAF both function in recruitment of the MSL complex that promotes X chromosome dosage compensation. Keywords: transcription factors, chromatin, Drosophila, dosage compensation