LAUSR

Nucleoporins regulate nuclear transport and are also involved in DNA damage, repair, cell cycle, chromatin organization, and gene expression. Here, we studied the role of nucleoporin Nup93 and the chromatin organizer CTCF in regulating HOXA expression during differentiation. ChIP sequencing revealed a significant overlap between Nup93 and CTCF peaks. Interestingly, Nup93 and CTCF are associated with the 3' and 5'HOXA genes respectively. Depletions of Nup93 and CTCF antagonistically modulate expression levels of 3'and 5'HOXA genes in undifferentiated NT2/D1 cells. Nup93 also regulates the localization of the HOXA gene locus, which disengages from the nuclear periphery upon Nup93 but not CTCF depletion, consistent with its upregulation. The dynamic association of Nup93 and CTCF with the HOXA locus during differentiation correlates with its spatial positioning and expression. While Nup93 tethers the HOXA locus to the nuclear periphery, CTCF potentially regulates looping of the HOXA gene cluster in a temporal manner. In summary, Nup93 and CTCF complement one another in modulating the spatiotemporal dynamics and function of the HOXA gene locus during differentiation.