Fundamental insights into the correlation between chromosome configuration and transcription

Abstract

Eukaryotic chromosomes exhibit a hierarchical organization that spans a spectrum of length scales, ranging from sub-regions known as loops, which typically comprise hundreds of base pairs, to much larger chromosome territories that can encompass a few mega base pairs. Chromosome conformation capture experiments that involve high-throughput sequencing methods combined with microscopy techniques have enabled a new understanding of inter- and intra-chromosomal interactions with unprecedented details. This information also provides mechanistic insights on the relationship between genome architecture and gene expression. In this article, we review the recent findings on three-dimensional interactions among chromosomes at the compartment, topologically associating domain (TAD), and loop levels and the impact of these interactions on the transcription process. We also discuss current understanding of various biophysical processes involved in multi-layer structural organization of chromosomes. Then, we discuss the relationships between gene expression and genome structure from perturbative genome-wide association studies. Furthermore, for a better understanding of how chromosome architecture and function are linked, we emphasize the role of epigenetic modifications in the regulation of gene expression. Such an understanding of the relationship between genome architecture and gene expression can provide a new perspective on the range of potential future discoveries and therapeutic research.

Polymer Model Unveils Quantitative Association of Chromatin Conformation and Gene Regulation

“…One of the experimental approaches to elucidating the relationship between genome structure and function is through the rearrangement of topological associating domain (TAD) boundaries. Deletions, inversions, or duplications of TAD boundaries are often created to disrupt the genome organization and then quantify the respective gene misexpression [16], [17]. In this study, we take a specific example of TAD boundary deletion to modify the genomic structure, and apply our computational framework to predict the gene expression level corresponding to this change.…”

“…Deletions, inversions, or duplications of TAD boundaries are often created to disrupt the genome organization and then quantify the respective gene misexpression [16], [17]. In this study, we take a specific example of TAD boundary deletion to modify the genomic structure, and apply our computational framework to predict the gene expression level corresponding to this change.…”