Journal Article

Dissecting the contribution of transposable elements to interphase chromosome structure

Babarinde, Isaac A., Fu, Xiuling, Xiao, Zhen, Hutchins, Andrew P., Sun, Li, Huang, Zhuoqi, Ma, Gang, Zhou, Xuemeng, He, Jiangping, Strunnikov, Alexander, Shi, Liyang

2026

Overview

Background Transposable elements (TEs) occupy nearly half of the human genome and play diverse biological roles. Despite their abundance, the extent to which TEs contribute to three-dimensional (3D) genome structure remains unclear. Results To investigate this, we generate a modified Hi-C analysis pipeline to probe TE-associated chromatin interactions. Our analysis reveals that TE sequences are responsible for 3D genome structure in interphase nuclei. This phenomenon is mediated by the recruitment of specific epigenetic/transcription factors to TEs, which both promote and impair chromatin contacts. We computationally identified known factors positively associated with chromatin contacts (CTCF, RAD21, SMC3) and chromatin contact impairing proteins (RNF2). Additionally, we identiy potential novel factors (SMARCA4, MAFK), which, when knocked down, lead to decreased chromatin contacts and loops at and between TEs. Notably, SMARCA4 knockdown selectively reduce short-range contacts, highlighting its role in maintaining 3D genome structure through TE binding. Conclusions Overall, our findings demonstrate that TEs are crucial determinants of 3D genome organization in mammalian cells. Key findings TEs alone determine 30% of the 3D genome structure, and 78% if heterotypic contacts are included. A/B compartments, and TADs, can be retrieved using TE-mapped reads only. ETFs can be divided into contact-positive and contact-negative factors at TEs. SMARCA4 and MAFK promote chromatin contacts between TE sequences.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: 3D genome / Animal Genetics and Genomics / BAF complex / Binding sites / Bioinformatics / Biomedical and Life Sciences / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromosome Structures / Chromosomes / DNA Helicases - genetics / DNA Helicases - metabolism / DNA Transposable Elements / Epigenesis, Genetic / Epigenetics / Evolutionary Biology / genome / Genome, Human / Genomes / Human Genetics / Humans / Interphase / Interphase - genetics / Life Sciences / Mammalian cells / Microbial Genetics and Genomics / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / Plant Genetics and Genomics / SMARCA4 / Stem cells / Transcription factors / Transcription Factors - genetics / Transcription Factors - metabolism / Transposable elements / Transposons