Abstract
BackgroundHox transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans. While the different Hox family members show clear functional specificity in vivo, they all show similar binding specificity in vitro and a satisfactory understanding of in vivo Hox target selectivity is still lacking.ResultsUsing transient transfection in Kc167 cells, we systematically analyze the binding of all eight Drosophila Hox proteins. We find that Hox proteins show considerable binding selectivity in vivo even in the absence of canonical Hox cofactors Extradenticle and Homothorax. Hox binding selectivity is strongly associated with chromatin accessibility, being highest in less accessible chromatin. Individual Hox proteins exhibit different propensities to bind less accessible chromatin, and high binding selectivity is associated with high-affinity binding regions, leading to a model where Hox proteins derive binding selectivity through affinity-based competition with nucleosomes. Extradenticle/Homothorax cofactors generally facilitate Hox binding, promoting binding to regions in less accessible chromatin but with little effect on the overall selectivity of Hox targeting. These cofactors collaborate with Hox proteins in opening chromatin, in contrast to the pioneer factor, Glial cells missing, which facilitates Hox binding by independently generating accessible chromatin regions.ConclusionsThese studies indicate that chromatin accessibility plays a key role in Hox selectivity. We propose that relative chromatin accessibility provides a basis for subtle differences in binding specificity and affinity to generate significantly different sets of in vivo genomic targets for different Hox proteins.
Highlights
Hox transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans
Hox selectivity We examined the relationship between chromatin accessibility and the selectivity of Hox binding, as measured by the number of different Hox proteins binding to any particular region
Our studies reveal a strong link between chromatin accessibility and target selection by Hox proteins
Summary
Hox transcription factors specify segmental diversity along the anterior-posterior body axis in metazoans. While the different Hox family members show clear functional specificity in vivo, they all show similar binding specificity in vitro and a satisfactory understanding of in vivo Hox target selectivity is still lacking. A clear example of our inadequate understanding of in vivo targeting of transcription factors is provided by the Hox class of homeodomain proteins. This highly conserved family of transcription factors direct the development of different segmental morphologies along the metazoan anterior-posterior axis, with the classic example of the Drosophila Hox gene Ultrabithorax (Ubx) specifying development of the haltere balancer organ in the third thoracic segment which, in the absence of Ubx, develops as a wing (reviewed in [5,6,7]). A potential way out of this conundrum is provided by the cofactors Extradenticle (Exd) and Porcelli et al Genome Biology (2019) 20:115
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have