Homotypic Transposable Element Pairing May Drive Coherent Chromatin Folding

Background/Objectives: Transposable elements comprise over 50% of the human genome, yet their role in chromatin organization is insufficiently studied. This study was motivated by the hypothesis that transposable elements drive chromatin contacts through homotypic coupling-that is, pairs of identical TEs physically pull genomic regions together. Methods: Analyzing public Micro-C and Hi-C datasets, I compared focal contact areas that stand out from low backgrounds against contact-depleted regions at kilobase resolution. Results: I discovered that transposable elements show enrichment at these focal contact points and even stronger depletion in contact-poor regions. Ancient mammalian transposable element families (MIR, L2) preferentially form homotypic pairs at chromatin contacts, while young primate-specific families (Alu, SVA) actively avoid homotypic pairing. The depletion of homotypic pairs in contact-poor regions exceeded their enrichment at focal contacts, suggesting that homotypically coupled transposable elements may be sequestered in protein-protected compartments. Unexpectedly, sequence-unrelated families like MIR and L2 showed similarly strong pairing behavior, indicating a mechanism independent of DNA sequence similarity. While my data demonstrates clear homotypic specificity patterns reproducible across cell types and individuals, it cannot distinguish whether transposable elements actively drive chromatin contacts or are passive markers of chromatin states. Conclusions: Study findings reveal previously uncharacterized patterns of transposable element organization at chromatin contact and suggest that homotypic pairing may provide anchoring points for coherent chromatin folding.