The 3D genome landscape: Diverse chromosomal interactions and their functional implications

Abstract

Genome organization includes contacts both within a single chromosome and between distinct chromosomes. Thus, regulatory organization in the nucleus may include interplay of these two types of chromosomal interactions with genome activity. Emerging advances in omics and single-cell imaging technologies have allowed new insights into chromosomal contacts, including those of homologs and sister chromatids, and their significance to genome function. In this review, we highlight recent studies in this field and discuss their impact on understanding the principles of chromosome organization and associated functional implications in diverse cellular processes. Specifically, we describe the contributions of intra-chromosomal, inter-homolog, and inter-sister chromatid contacts to genome organization and gene expression.

Keywords: 3D genome organization; development; gene regulation; homolog pairing; inter-chromosomal contacts; intra-chromosomal contacts; meiotic chromosomes; sister chromatids.

FIGURE 1

Nuclear inter-chromosomal interactions. (A) Chromosomes can occupy discrete territories with a tendency for neighboring chromosomes to intermingle. The left inset depicts an inter-chromosomal hub associated with open chromatin and active transcription with transcription factors (light gray spheres) and RNAs (medium gray). The right inset depicts an inter-chromosomal hub of heterochromatin with associated regulatory factors (dark gray spheres). (B) Schematic organization of mammalian meiotic chromosomes (pachynema; top panel), Drosophila somatic homologs (middle panel), and sister chromatids (bottom panel) with corresponding representations of cis and trans Hi-C contact maps. The meiotic trans contact map depicts inter-homolog contacts. Purple, maternal homolog (Mat); green, paternal homolog (Pat); respective shades of the homolog colors (top panel) or two shades of gray (bottom panel), sister chromatids; gray lines, synaptonemal complex (SC); black sphere, transcription-related clustering; black ellipsoid, regulators (insulators or architectural proteins).

FIGURE 2

Homolog pairing role during development and differentiation. Homolog pairing levels may act as a potential “switch” (gray) that could play a role in cell type-specific gene regulation. The pairing status can also be related to cell differentiation including the formation or maintenance of cellular identities. Schematic of paired (one black dot) or unpaired (two black dots) homologs in the nucleus (blue).