Role of Nup93 subcomplex in HOXA gene regulation during NT2/D1 differentiation

Abstract

Nuclear Pore complexes (NPCs) are multiprotein complexes embedded in the nuclear envelope that facilitate the regulated transport of RNA and proteins between nucleus and cytoplasm. NPCs consist of ~30 different types of nucleoporins. Recent evidences suggest an involvement of nucleoporins in regulation of gene expression and cell differentiation. Here we investigated the role of Nup93 subcomplex in the regulation of HOXA gene expression during differentiation of NTera2.D1 embryonal carcinoma cell line, which differentiates into a neuronal lineage in response to retinoic acid (RA). We show that Nup93 and CTCF antagonistically regulate HOXA gene expression. Nup93 shows an altered occupancy on HOXA gene promoters during differentiation. We also report for the first time the four copies of HOXA gene cluster are repositioned proximal to the nuclear periphery during RA mediated differentiation in the interphase nucleus. We have shown that the interactors of Nup93 subcomplex independently regulate HOXA gene expression. Taken together our data uncovers a novel role for Nup93 and CTCF in modulating the spatiotemporal localization and function of the HOXA gene locus during differentiation.