Erythrocytes 3D genome organization in vertebrates

Abstract

Generation of mature red blood cells, consisting mainly of hemoglobin, is a remarkable example of coordinated action of various signaling networks. Chromatin condensation is an essential step for terminal erythroid differentiation and subsequent nuclear expulsion in mammals. Here, we profiled 3D genome organization in the blood cells from ten species belonging to different vertebrate classes. Our analysis of contact maps revealed a striking absence of such 3D interaction patterns as loops or TADs in blood cells of all analyzed representatives. We also detect large-scale chromatin rearrangements in blood cells from mammals, birds, reptiles and amphibians: their contact maps display strong second diagonal pattern, representing an increased frequency of long-range contacts, unrelated to TADs or compartments. This pattern is completely atypical for interphase chromosome structure. We confirm that these principles of genome organization are conservative in vertebrate erythroid cells.

Figure 1

The key features of the erythrocytes’ genome organization on the example of chicken. (A) Hi-C contact heatmaps of erythrocytes (left) and a schematic representation of the map with the second diagonal marked (right). (B) Hi-C contact heatmaps of fibroblasts (left) and a schematic representation of the map (right). (C) The dependence of the contact probability on the genomic distance P(s) averaged over all chromosomes for chicken erythrocytes and fibroblasts. Bottom panel: derivatives of P(s) curves. Note that the shape of the curves differs in TADs typical size region and in the second diagonal region. Hi-C maps were visualized with Juicebox (version 1.11.08).

Figure 2

Contact frequency P(s) derived from Hi-C data obtained from chicken erythrocytes. Curves for genome average (all chrs) and long individual chromosomes are shown. The hump of the second diagonal is obvious on the first ~ six longest chromosomes. Bottom panel: derivatives of P(s) curves.

Figure 3

The phylogenetic tree of the species included in this study.

Figure 4

3D genome organization of erythrocytes in vertebrates. (A) Representative Hi-C heatmap of one of the long chromosomes for each species under analysis. (B) Chart of chromosome sizes depicted in (A). Hi-C maps were visualized with Juicebox (version 1.11.08).

Figure 5

The dependence of the contact probability on the genomic distance P(s) for erythrocytes and erythroblasts (human and mouse) averaged over all chromosomes for 10 species under analysis. Bottom panel: derivatives of P(s) curves.