skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on May 1, 2026

Title: Topologically associating domains and the evolution of three‐dimensional genome architecture in rice
SUMMARY We examined the nature and evolution of three‐dimensional (3D) genome conformation, including topologically associating domains (TADs), in five genomes within the genusOryza. These included three varieties from subspecies within domesticated Asian riceO. sativaas well as their closely related wild relativesO. rufipogonandO. meridionalis. We used the high‐resolution chromosome conformation capture technique Micro‐C, which we modified for use in rice. Our analysis of rice TADs shows that TAD boundaries have high transcriptional activity, low methylation levels, low transposable element (TE) content, and increased gene density. We also find a significant correlation of expression levels for genes within TADs, suggesting that they do function as genomic domains with shared regulatory features. Our findings indicate that animal and plant TADs may share more commonalities than were initially thought, as evidenced by similar genetic and epigenetic signatures associated with TADs and boundaries. To examine 3D genome divergence, we employed a computer vision‐based algorithm for the comparison of chromatin contact maps and complemented this analysis by assessing the evolutionary conservation of individual TADs and their boundaries. We conclude that overall chromatin organization is conserved in rice, and 3D structural divergence correlates with evolutionary distance between genomes. We also note that individual TADs are not well conserved, even at short evolutionary timescales.  more » « less
Award ID(s):
2204374
PAR ID:
10615771
Author(s) / Creator(s):
; ; ; ; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
The Plant Journal
Volume:
122
Issue:
4
ISSN:
0960-7412
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract The organization of chromatin into self-interacting domains is universal among eukaryotic genomes, though how and why they form varies considerably. Here we report a chromosome-scale reference genome assembly of pepper ( Capsicum annuum ) and explore its 3D organization through integrating high-resolution Hi-C maps with epigenomic, transcriptomic, and genetic variation data. Chromatin folding domains in pepper are as prominent as TADs in mammals but exhibit unique characteristics. They tend to coincide with heterochromatic regions enriched with retrotransposons and are frequently embedded in loops, which may correlate with transcription factories. Their boundaries are hotspots for chromosome rearrangements but are otherwise depleted for genetic variation. While chromatin conformation broadly affects transcription variance, it does not predict differential gene expression between tissues. Our results suggest that pepper genome organization is explained by a model of heterochromatin-driven folding promoted by transcription factories and that such spatial architecture is under structural and functional constraints. 
    more » « less
  2. Abstract BackgroundInhomogeneous patterns of chromatin-chromatin contacts within 10–100-kb-sized regions of the genome are a generic feature of chromatin spatial organization. These features, termed topologically associating domains (TADs), have led to the loop extrusion factor (LEF) model. Currently, our ability to model TADs relies on the observation that in vertebrates TAD boundaries are correlated with DNA sequences that bind CTCF, which therefore is inferred to block loop extrusion. However, although TADs feature prominently in their Hi-C maps, non-vertebrate eukaryotes either do not express CTCF or show few TAD boundaries that correlate with CTCF sites. In all of these organisms, the counterparts of CTCF remain unknown, frustrating comparisons between Hi-C data and simulations. ResultsTo extend the LEF model across the tree of life, here, we propose theconserved-current loop extrusion (CCLE) modelthat interprets loop-extruding cohesin as a nearly conserved probability current. From cohesin ChIP-seq data alone, we derive a position-dependent loop extrusion rate, allowing for a modified paradigm for loop extrusion, that goes beyond solely localized barriers to also include loop extrusion rates that vary continuously. We show that CCLE accurately predicts the TAD-scale Hi-C maps of interphaseSchizosaccharomyces pombe, as well as those of meiotic and mitoticSaccharomyces cerevisiae, demonstrating its utility in organisms lacking CTCF. ConclusionsThe success of CCLE in yeasts suggests that loop extrusion by cohesin is indeed the primary mechanism underlying TADs in these systems. CCLE allows us to obtain loop extrusion parameters such as the LEF density and processivity, which compare well to independent estimates. 
    more » « less
  3. Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce. To capture the macroevolutionary diversity of vertebrate chromatin conformation, here we generate de novo genome assemblies for two cryptodiran (hidden-neck) turtles via Illumina sequencing, chromosome conformation capture, and RNA-seq:Apalone spinifera(ZZ/ZW, 2n= 66) andStaurotypus triporcatus(XX/XY, 2n= 54). We detected differences in the three-dimensional (3D) chromatin structure in turtles compared to other amniotes beyond the fusion/fission events detected in the linear genomes. Namely, whole-genome comparisons revealed distinct trends of chromosome rearrangements in turtles: (1) a low rate of genome reshuffling inApalone(Trionychidae) whose karyotype is highly conserved when compared to chicken (likely ancestral for turtles), and (2) a moderate rate of fusions/fissions inStaurotypus(Kinosternidae) andTrachemys scripta(Emydidae). Furthermore, we identified a chromosome folding pattern that enables “centromere–telomere interactions” previously undetected in turtles. The combined turtle pattern of “centromere–telomere interactions” (discovered here) plus “centromere clustering” (previously reported in sauropsids) is novel for amniotes and it counters previous hypotheses about amniote 3D chromatin structure. We hypothesize that the divergent pattern found in turtles originated from an amniote ancestral state defined by a nuclear configuration with extensive associations among microchromosomes that were preserved upon the reshuffling of the linear genome. 
    more » « less
  4. Dunbrack, Roland L (Ed.)
    Chromatin is a polymer complex of DNA and proteins that regulates gene expression. The three-dimensional (3D) structure and organization of chromatin controls DNA transcription and replication. High-throughput chromatin conformation capture techniques generate Hi-C maps that can provide insight into the 3D structure of chromatin. Hi-C maps can be represented as a symmetric matrix A i j , where each element represents the average contact probability or number of contacts between chromatin lociiandj. Previous studies have detected topologically associating domains (TADs), or self-interacting regions in A i j within which the contact probability is greater than that outside the region. Many algorithms have been developed to identify TADs within Hi-C maps. However, most TAD identification algorithms are unable to identify nested or overlapping TADs and for a given Hi-C map there is significant variation in the location and number of TADs identified by different methods. We develop a novel method to identify TADs, KerTAD, using a kernel-based technique from computer vision and image processing that is able to accurately identify nested and overlapping TADs. We benchmark this method against state-of-the-art TAD identification methods on both synthetic and experimental data sets. We find that the new method consistently has higher true positive rates (TPR) and lower false discovery rates (FDR) than all tested methods for both synthetic and manually annotated experimental Hi-C maps. The TPR for KerTAD is also largely insensitive to increasing noise and sparsity, in contrast to the other methods. We also find that KerTAD is consistent in the number and size of TADs identified across replicate experimental Hi-C maps for several organisms. Thus, KerTAD will improve automated TAD identification and enable researchers to better correlate changes in TADs to biological phenomena, such as enhancer-promoter interactions and disease states. 
    more » « less
  5. Abstract Chromatin looping is important for gene regulation, and studies of 3D chromatin structure across species and cell types have improved our understanding of the principles governing chromatin looping. However, 3D genome evolution and its relationship with natural selection remains largely unexplored. In mammals, the CTCF protein defines the boundaries of most chromatin loops, and variations in CTCF occupancy are associated with looping divergence. While many CTCF binding sites fall within transposable elements (TEs), their contribution to 3D chromatin structural evolution is unknown. Here we report the relative contributions of TE-driven CTCF binding site expansions to conserved and divergent chromatin looping in human and mouse. We demonstrate that TE-derived CTCF binding divergence may explain a large fraction of variable loops. These variable loops contribute significantly to corresponding gene expression variability across cells and species, possibly by refining sub-TAD-scale loop contacts responsible for cell-type-specific enhancer-promoter interactions. 
    more » « less