scholarly journals Epigenomic and 3D genome architecture in naïve and primed human embryonic stem cell states

2017 ◽  
Author(s):  
Stephanie L. Battle ◽  
Naresh Doni Jayavelu ◽  
Robert N. Azad ◽  
Jennifer Hesson ◽  
Faria N. Ahmed ◽  
...  
Keyword(s):  
Human Embryonic Stem Cell ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Genome Architecture ◽  
Open Chromatin ◽  
Substantial Portion ◽  
3D Genome ◽  
Mammalian Embryogenesis ◽  
Post Implantation ◽  
Epigenomic Reprogramming

ABSTRACTDuring mammalian embryogenesis changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the pre-implantation blastocyst (naïve) and post-implantation epiblast (primed), our data demonstrate that a substantial portion of known human enhancers are pre-marked by H3K4me1 in naïve cells, providing an enhanced open chromatin state in naïve pluripotency. The naïve enhancer repertoire occupies nine percent of the genome, three times that of primed cells, and can exist in broad chromatin domains over fifty kilobases. Enhancer chromatin states are largely poised. Seventy-seven percent of naïve enhancers are decommissioned in a stepwise manner as cells become primed. While primed topological associated domains are unaltered upon differentiation, naïve domains expand across primed boundaries, impacting three dimensional genome architecture. Differential topological associated domain edges coincide with naïve H3K4me1 enrichment. Our results suggest that naïve-derived cells have a chromatin landscape reflective of early embryogenesis.

scholarly journals Enhancer Chromatin and 3D Genome Architecture Changes from Naive to Primed Human Embryonic Stem Cell States

2019 ◽  
Vol 12 (5) ◽  
pp. 1129-1144 ◽  
Author(s):  
Stephanie L. Battle ◽  
Naresh Doni Jayavelu ◽  
Robert N. Azad ◽  
Jennifer Hesson ◽  
Faria N. Ahmed ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Genome Architecture ◽  
3D Genome

scholarly journals Using three-dimensional regulatory chromatin interactions from adult and fetal cortex to interpret genetic results for psychiatric disorders and cognitive traits

2018 ◽  
Author(s):  
Paola MD Giusti-Rodriguez ◽  
Patrick F Sullivan
Keyword(s):  
Psychiatric Disorders ◽  
Association Studies ◽  
Three Dimensional ◽  
Fetal Brain ◽  
Autism Spectrum ◽  
Open Chromatin ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
3D Genome ◽  
Cognitive Traits

Genome-wide association studies have identified hundreds of genetic associations for complex psychiatric disorders and cognitive traits. However, interpretation of most of these findings is complicated by the presence of many significant and highly correlated genetic variants located in non-coding regions. Here, we address this issue by creating a high-resolution map of the three-dimensional (3D) genome organization by applying Hi-C to adult and fetal brain cortex with concomitant RNA-seq, open chromatin (ATAC-seq), and ChIP-seq data (H3K27ac, H3K4me3, and CTCF). Extensive analyses established the quality, information content, and salience of these new Hi-C data. We used these data to connect 938 significant genetic loci for schizophrenia, intelligence, ADHD, alcohol dependence, Alzheimer's disease, anorexia nervosa, autism spectrum disorder, bipolar disorder, major depression, and educational attainment to 8,595 genes (with 42.1% of these genes implicated more than once). We show that assigning genes to traits based on proximity provides a limited view of the complexity of GWAS findings and that gene set analyses based on functional genomic data provide an expanded view of the biological processes involved in the etiology of schizophrenia and other complex brain traits.

scholarly journals SARS-CoV-2 Restructures the Host Chromatin Architecture

2021 ◽  
Author(s):  
Ruoyu Wang ◽  
Joo-Hyung Lee ◽  
Feng Xiong ◽  
Jieun Kim ◽  
Lana Al Hasani ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Host Cells ◽  
Interferon Response ◽  
Genome Architecture ◽  
3D Genome ◽  
Chromatin Architecture ◽  
Severe Infections ◽  
Global Reduction ◽  
Host Chromatin

SARS-CoV-2 has made >190-million infections worldwide, thus it is pivotal to understand the viral impacts on host cells. Many viruses can significantly alter host chromatin, but such roles of SARS-CoV-2 are largely unknown. Here, we characterized the three-dimensional (3D) genome architecture and epigenome landscapes in human cells after SARS-CoV-2 infection, revealing remarkable restructuring of host chromatin architecture. High-resolution Hi-C 3.0 uncovered widespread A compartmental weakening and A-B mixing, together with a global reduction of intra-TAD chromatin contacts. The cohesin complex, a central organizer of the 3D genome, was significantly depleted from intra-TAD regions, supporting that SARS-CoV-2 disrupts cohesin loop extrusion. Calibrated ChIP-Seq verified chromatin restructuring by SARS-CoV-2 that is particularly manifested by a pervasive reduction of euchromatin modifications. Built on the rewired 3D genome/epigenome maps, a modified activity-by-contact model highlights the transcriptional weakening of antiviral interferon response genes or virus sensors (e.g., DDX58) incurred by SARS-CoV-2. In contrast, pro-inflammatory genes (e.g. IL-6) high in severe infections were uniquely regulated by augmented H3K4me3 at their promoters. These findings illustrate how SARS-CoV-2 rewires host chromatin architecture to confer immunological gene deregulation, laying a foundation to characterize the long-term epigenomic impacts of this virus.

Three-dimensional growth matrix for human embryonic stem cell-derived neuronal cells

2012 ◽  
Vol 8 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Laura Ylä-Outinen ◽  
Tiina Joki ◽  
Mari Varjola ◽  
Heli Skottman ◽  
Susanna Narkilahti
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Human Embryonic Stem Cell ◽  
Neuronal Cells ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Dimensional Growth

scholarly journals Defective chromatin architectures in embryonic stem cells derived from somatic cell nuclear transfer impair their differentiation potentials

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Dan-Ya Wu ◽  
Xinxin Li ◽  
Qiao-Ran Sun ◽  
Cheng-Li Dou ◽  
Tian Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Somatic Cell ◽  
Genome Organization ◽  
Nuclear Transfer ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Differentiation Potential ◽  
3D Genome

AbstractNuclear transfer embryonic stem cells (ntESCs) hold enormous promise for individual-specific regenerative medicine. However, the chromatin states of ntESCs remain poorly characterized. In this study, we employed ATAC-seq and Hi-C techniques to explore the chromatin accessibility and three-dimensional (3D) genome organization of ntESCs. The results show that the chromatin accessibility and genome structures of somatic cells are re-arranged to ESC-like states overall in ntESCs, including compartments, topologically associating domains (TADs) and chromatin loops. However, compared to fertilized ESCs (fESCs), ntESCs show some abnormal openness and structures that have not been reprogrammed completely, which impair the differentiation potential of ntESCs. The histone modification H3K9me3 may be involved in abnormal structures in ntESCs, including incorrect compartment switches and incomplete TAD rebuilding. Moreover, ntESCs and iPSCs show high similarity in 3D genome structures, while a few differences are detected due to different somatic cell origins and reprogramming mechanisms. Through systematic analyses, our study provides a global view of chromatin accessibility and 3D genome organization in ntESCs, which can further facilitate the understanding of the similarities and differences between ntESCs and fESCs.

scholarly journals Three-dimensional organization of chromatin associated RNAs and their role in chromatin architecture in human cells

2021 ◽  
Author(s):  
Riccardo Calandrelli ◽  
Xingzhao Wen ◽  
Tri C. Nguyen ◽  
Chien-Ju Chen ◽  
Zhijie Qi ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Myelogenous Leukemia ◽  
Leukemia Cells ◽  
Chromatin Loops ◽  
3D Genome ◽  
Vital Component ◽  
Genome Interactions ◽  
Global Reduction

Chromatin-associated RNA (caRNA) is a vital component of the interphase nucleus; yet its distribution and role in the 3D genome organization remain poorly understood. Here, we map caRNA's spatial distribution on the 3D genome in human embryonic stem cells, fibroblasts, and myelogenous leukemia cells. We find that the relative abundance of trans-acting caRNA on DNA reflects the 3D compartmentalization, and the caRNA's sequence is predictive of its spatial localization. We observe localized caRNA-genome interactions that span several hundred kilobases to several megabases. These caRNA domains correlate with chromatin loops and enhancer-promoter interactions. Global reduction of caRNA abundance increases the number of chromatin loops and strengths, which could be reversed by suppression of caRNA's electrostatic interactions. These results indicate that caRNA regulates chromatin looping, at least in part through RNA's electrostatic interactions.

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