Regulation of the three-dimensional chromatin organization by transposable elements in pig spleen

Abstract

Like other mammalian species, the pig genome is abundant with transposable elements (TEs). The importance of TEs for three-dimensional (3D) chromatin organization has been observed in species like human and mouse, yet current understanding about pig TEs is absent. Here, we investigated the contribution of TEs for the 3D chromatin organization in three pig tissues, focusing on spleen which is crucial for both adaptive and innate immunity. We identified dozens of TE families overrepresented with CTCF binding sites, including LTR22_SS, LTR15_SS and LTR16_SSc which are pig-specific families of endogenous retroviruses (ERVs). Interestingly, LTR22_SS elements harbor a CTCF motif and create hundreds of CTCF binding sites that are associated with adaptive immunity. We further applied Hi-C to profile the 3D chromatin structure in spleen and found that TE-derived CTCF binding sites correlate with chromatin insulation and frequently overlap TAD borders and loop anchors. Notably, one LTR22_SS-derived CTCF binding site demarcate a TAD boundary upstream of XCL1, which is a spleen-enriched chemokine gene important for lymphocyte trafficking and inflammation. Overall, this study represents a first step toward understanding the function of TEs on 3D chromatin organization regulation in pigs and expands our understanding about the functional importance of TEs in mammals.