Select Hox factors can bind inaccessible chromatin with and/or without the help of common co-factors. (A) Diagram summarizing the genomic DNA binding activities of Hox TFs in Drosophila Kc167 cells (data from Beh et al., 2016; Porcelli et al., 2019). By comparing the chromatin accessibility profiles of cells prior to Hox factor transfection and genome binding profiles after Hox factor transient transfection in Kc167 cells, Beh et al. and Porcelli et al. demonstrated that anterior factors and posterior Drosophila factors tend to have the ability to bind inaccessible chromatin (Beh et al., 2016; Porcelli et al., 2019). Furthermore, Exd and Hth expression tend to enhance a factor’s ability to bind to inaccessible chromatin (Beh et al., 2016; Porcelli et al., 2019). It is important to note that the ability to bind inaccessible chromatin of Abd-B was not enhanced and the ability of Scr was only slightly enhanced by Exd/Hth. (B) Diagram summarizing the genomic DNA binding activities of human Hox factors in motor neuron cells (Bulajić et al., 2020), mouse embryonic stem cells (Singh et al., 2021), and mouse limb buds (Desanlis et al., 2020). The genomic binding and accessibility profiles were intersected to assess inaccessible chromatin binding. Nearby PBX and MEIS motifs were used to determine co-binding. Drosophila and human Hox factors follow a similar trend that posterior factors can bind inaccessible chromatin more so than central factors.