Integrating 3D chromatin interactions in the transcriptional regulation of genes that respond to chromatin stresses
2024
Iglesia Mirones, Miguel la | Gallego Jiménez, Alicia | Pérez Cantalapiedra, Carlos
The implication of three-dimensional (3D) genome structure in the transcriptional process of genes is a key regulatory layer within the cell nucleus. Although this regulation has been described in multiple resolutions, the understanding of the phenotypic consequences of chromatin structure alteration and the underlying transcriptional mechanisms remains incomplete. In this work, we investigated the chromatin structure in wild-type (WT) mouse embryonic stem cells (mESCs) of several gene clusters previously identified based on their similar transcriptional response to chromatin stresses. Specifically, we studied the distribution of these gene clusters in the A/B compartments and within the Topologically Associated Domains (TADs), examining the specificity, density, and size of the TADs. Additionally, chromatin interactions of their promoters were extracted and analyzed using genome-wide contact maps from High Throughput Chromosome Conformation Capture (Hi-C) and Promoter Capture Hi-C (PC-HiC) techniques. Our findings reveal that genes in cluster 1A and cluster 2 display a distinct chromatin architecture marked by closer spatial proximity within each cluster, resembling the spatiotemporally specific and constitutively active patterns of gene expression, respectively. Additionally, genes in cluster 3 display a more heterogeneous 3D chromatin structure, which could explain the mixed transcriptional responses observed in this cluster. Taken together, this work sheds light on the contribution of the 3D genome architecture in gene regulation and the complex mechanisms underlying the transcriptional response to chromatin alterations.
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