Virus Infection Induces Immune Gene Activation with CTCF Anchored Enhancers and Chromatin Interactions in Pig Genome.

Abstract

Chromatin organization is important for gene transcription in pig genome. However, its three-dimensional (3D) structure and dynamics are much less investigated than those in human. Here we applied the long-reads chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) method to map the whole-genome chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase Ⅱ (RNAPⅡ or POLⅡ) in porcine macrophage cells before and after polyinosinic-polycytidylic acid [Poly(I:C)] induction. Our results revealed that Poly(I:C) induction impacts the 3D genome organization in the 3D4/21 cells at the fine-scale chromatin loop level rather than at the large-scale domain level. Furthermore, our findings underscored the pivotal role of CTCF anchored chromatin interactions in reshaping chromatin architecture during immune responses. Knock-out of the CTCF locus further confirmed that the CTCF anchored enhancers are associated with the activation of immune genes via long-range interactions. Notably, ChIA-PET data also supported the spatial relationship between single nucleotide polymorphisms (SNPs) and the related gene transcription in 3D genome aspect. Our findings in this study provide new clues and potential targets to explore key elements related to diseases in swine and are also likely to shed light on elucidating chromatin organization and dynamics underlying the process of mammalian infectious diseases.