TY  - JOUR
A1  - Wang, Liangxi
A1  - Taylor, Tiegh
A1  - Rathnakumar, Kumaragurubaran
A1  - Khyzha, Nadiya
A1  - Liang, Minggao
A1  - Alizada, Azad
A1  - Campitelli, Laura F.
A1  - Pour, Sara E.
A1  - Patel, Zain M.
A1  - Antounians, Lina
A1  - Tobias, Ian C.
A1  - Hou, Huayun
A1  - Hughes, Timothy R.
A1  - Roy, Sushmita
A1  - Mitchell, Jennifer A.
A1  - Fish, Jason E.
A1  - Wilson, Michael D.
T1  - Multi-species analysis of inflammatory response elements reveals ancient and lineage-specific contributions of transposable elements to NF-kB binding
Y1  - 2025/07/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1544 
EP  - 1559 
DO  - 10.1101/gr.280357.124 
VL  - 35 
IS  - 7 
UR  - http://genome.cshlp.org/content/35/7/1544.abstract 
N2  - Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we perform a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA ChIP-seq data from TNF-stimulated primary aortic endothelial cells isolated from human, mouse, and cow, we find that 55 TE subfamilies are associated with RELA-bound regions, many of which reside near TNF-responsive genes. A prominent example of lineage-specific contribution of transposons comes from the bovine SINE subfamilies Bov-tA1/2/3 which collectively contributed over 14,000 RELA-bound regions in cow. By comparing RELA binding data across species, we also find several examples of RELA motif-bearing TEs that colonized the genome prior to the divergence of the three species and contributed to species-specific RELA binding. For example, we find human RELA-bound MER81 instances are enriched for the interferon gamma pathway and demonstrate that one RELA-bound MER81 element can control the TNF-induced expression of interferon gamma receptor 2 (IFNGR2). Using ancestral reconstructions, we find that RELA containing MER81 instances rapidly decayed during early primate evolution (>50 million years ago [MYA]) before stabilizing since the separation of Old World monkeys (<50 MYA). Taken together, our results suggest ancient and lineage-specific transposon subfamilies contributed to mammalian NF-kB regulatory networks. 
ER  -