Dataset Information

Remodeling of 3D Gene Architecture in Myocardium from Embryonic Development to Early Aging [Hi-C]

ABSTRACT: Heart-related diseases are increasingly attacking the younger population, and getting more prevalent as the population ages. Better understanding of heart development and aging could help decipher the mechanism of associated heart diseases. In this study, we reported the application of a typical miniature swine -- Tibetan pig, as human heart model, and illustrated the changes in higher-order chromatin structure and transcription regulation from fetal to sexual maturity and early senescence, as well as the role they play in physiological development and aging. We observed altered multi-scale structures of the 3D genome from territories and A/B compartments to TADs and loops/PEIs. Changes in territories and A/B compartments indicate high plasticity and disorganization of chromatin structure for the fetal and senescent stages, respectively, compared to the more ordered conformation for the young adult stage, embodied by Von Neumann Entropy (VNE) and compartmentalization strength indexes. From such coarse scale, we also observed that heterochromatin gradually stacked and relaxed during development and senescence, supported by evidence of change in intensity of B-B interactions and correlation between sequence features and A/B compartment switches, across the three critical stages. A finer examination of TAD and loops/PEIs showed that young adults tend to have more accurate transcription regulation through finer control of chromatin structure dynamics, supported by higher correlation of gene expression and TAD connectivity, more space between dynamic boundaries and their targeted genes, and stronger ‘loop skew’ towards A compartments. Another observation of monotonic increase in long-range interactions and decrease in short-range interactions throughout the development and senescent process indicates the gradual loss of plasticity for chromatin conformation.

ORGANISM(S): Sus scrofa

PROVIDER: GSE247657 | GEO | 2025/11/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The 3D genome organization is mediated by chromatin architectural elements such as insulator binding proteins and cohesin and serves as a crucial epigenetic regulatory mechanism. In Drosophila, architectural proteins translocate from chromatin to the nucleoplasm in response to hyperosmotic stress forming condensates known as insulator bodies, which exhibit liquid-liquid phase separation (LLPS) features. We harnessed the osmotic stress response to gain insights into the differences in genome organization principles between human and fly genomes across several scales. We found that under identical osmotic stress conditions, CTCF also translocates to the nucleoplasm in human cells but does not form condensates. Using genome-wide chromosome conformation capture (Hi-C), we found that in both human and Drosophila, osmotic stress induces a loss of genome structure, characterized by the loss of compartments and the weakening of TAD boundary strength throughout the genome, as well as a significant increase in cross-compartment interactions in the long-range. In both Drosophila and human genomes, looping interactions are also lost during stress. The genome organization in human cells almost fully recovers after 1 hour in normal media post osmotic stress, regaining full compartment structure, TAD boundary strength and loop formation. Recovery of Drosophila cells after 1 hour in normal media, however, is incomplete as genomes fail to regain normal compartment structure and TAD boundary strength remains significantly reduced. Interestingly, loops are re-formed at this time point. Analysis of these differences revealed that the Drosophila genome does not replicate the canonical A/B compartment organization found in vertebrates. In Drosophila, A compartments engage in A-to-A long-range interactions in a manner similar to that found in the human genome. However, long range B-B interactions are rarely observed. Interestingly, A compartments are specifically enriched in γH2Av and Su(Hw) insulator proteins, suggesting that the LLPS properties of these proteins may be required for compartment formation.

Dataset Information

Remodeling of 3D Gene Architecture in Myocardium from Embryonic Development to Early Aging [Hi-C]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets