Chromatin accessibility plays a key role in selective targeting of Hox proteins.
MetadataShow full item record
Porcelli, D., Fischer, B., Russell, S., & White, R. (2019). Chromatin accessibility plays a key role in selective targeting of Hox proteins.. Genome biology, 20 (1), 115. https://doi.org/10.1186/s13059-019-1721-4
Background 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. Results Using transient transfection in Kc167 cells, we systematically analyse 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. Conclusions These 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.
Cell Line, Chromatin, Animals, Drosophila, Homeodomain Proteins, Drosophila Proteins, Transcription Factors, Chromatin Assembly and Disassembly, Amino Acid Motifs
The work was supported by the Biotechnology and Biological Sciences Research Council (Grant BB/M007081/1)
Embargo Lift Date
External DOI: https://doi.org/10.1186/s13059-019-1721-4
This record's URL: https://www.repository.cam.ac.uk/handle/1810/293062
All rights reserved