Three-dimensional chromatin architecture datasets for aging and Alzheimer’s disease

Meng, Guofeng; Xu, Hong; Lu, Dong; Li, Shensuo; Zhao, Zhenzhen; Li, Haohao; Zhang, Weidong

doi:10.1038/s41597-023-01948-z

Cited by 9 publications

(8 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S4). Additionally, several independent studies have also demonstrated chromosomal interactions within this APOE locus [43,44]. Our findings suggest that these four APOE locus genes are located within a single TAD, creating a 3D genomic environment that facilitates their coregulation.…”

Section: D Genome Structure Of the Apoe Locussupporting

confidence: 60%

See 1 more Smart Citation

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Lee¹,

Leong²,

Chen³

et al. 2023

Preprint

View full text Add to dashboard Cite

The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

show abstract

Section: D Genome Structure Of the Apoe Locussupporting

confidence: 60%

“…Recently, research in AD has applied this concept [75,76]. Based on evidence from chromosome conformation capture [42][43][44], it is likely that multiple genes within the APOE locus are coregulated within the same TAD. Therefore, TADs are well-suited to study the mechanisms of of multiple genes within APOE locus.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Lee¹,

Leong²,

Chen³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…By deleting a microglia‐specific enhancer 30 kb upstream of BIN1 promoter, they observed a reduced BIN1 expression in microglia, but not in neurons or astrocytes. In another study, Hi‐C was performed on AD brain samples and a notable enrichment of chromatin loops upstream of the BIN1 promoter overlapping AD risk variants was reported, lending further support to the existence of long‐range regulatory mechanisms related to BIN1 106 . In a very recent study, analysis of snRNA‐seq and Hi‐C from AD brain samples revealed increased somatic mosaic gene fusion events due to DNA double stranded breaks (DSBs) in excitatory neurons.…”

Section: Single‐nucleus Transcriptomics Elucidates Cell Type–specific...mentioning

confidence: 84%

Gene networks and systems biology in Alzheimer's disease: Insights from multi‐omics approaches

Rahimzadeh,

Srinivasan,

Zhang

et al. 2024

Alzheimer's & Dementia

View full text Add to dashboard Cite

Despite numerous studies in the field of dementia and Alzheimer's disease (AD), a comprehensive understanding of this devastating disease remains elusive. Bulk transcriptomics have provided insights into the underlying genetic factors at a high level. Subsequent technological advancements have focused on single‐cell omics, encompassing techniques such as single‐cell RNA sequencing and epigenomics, enabling the capture of RNA transcripts and chromatin states at a single cell or nucleus resolution. Furthermore, the emergence of spatial omics has allowed the study of gene responses in the vicinity of amyloid beta plaques or across various brain regions. With the vast amount of data generated, utilizing gene regulatory networks to comprehensively study this disease has become essential. This review delves into some techniques employed in the field of AD, explores the discoveries made using these techniques, and provides insights into the future of the field.

show abstract

“…The maturation of chromatin conformation capture technology such as HiC has enabled the association of genomically distal CREs to genes through their spatial proximity in nuclei to target-gene promoters (Rao et al 2014; Javierre et al 2016; Kloetgen et al 2020; Xu et al 2022; Meng et al 2023). The high resource usage is one of the key limitations of these approaches.…”

Section: Introductionmentioning

confidence: 99%

DegCre: Probabilistic association of differential gene expression with regulatory regions

Roberts,

Cooper,

Myers

2023

Preprint

View full text Add to dashboard Cite

Differential gene expression in response to perturbations is mediated at least in part by changes in binding of transcription factors (TFs) and other proteins at specific genomic regions. Association of these cis-regulatory elements (CREs) with their target genes is a challenging task that is essential to address many biological and mechanistic questions. Many current approaches rely on chromatin conformation capture techniques that identify spatial proximity between genomic sites to establish CRE-to-gene associations. These methods can be effective but have limitations, including resolution, minimal detectable interaction distance, and cost. As an alternative, we have developed DegCre, a non-parametric method that evaluates correlations between measurements of perturbation-induced differential gene expression and differential regulatory signal at CREs to score possible CRE-to-gene associations. It has several unique features, including the ability to: use any type of CRE activity measurement; yield probabilistic scores for CRE-to-gene pairs; and assess CRE-to-gene pairings across a wide range of sequence distances. We apply DegCre to three data sets, each employing different perturbations and containing a variety of regulatory signal measurements, including chromatin openness, histone modifications, and TF occupancy. To test their efficacy, we compare DegCre associations to HiC loop calls and to CRISPR validated interactions, with both yielding good agreement. We demonstrate the identification of perturbation direct target genes with DegCre confirm the results with previous reports. DegCre is a novel approach to the association of CREs to genes from a perturbation-differential perspective, with strengths that are complementary to existing approaches and allow for new insights into gene regulation.

show abstract

Three-dimensional chromatin architecture datasets for aging and Alzheimer’s disease

Cited by 9 publications

References 58 publications

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Mitochondrial Function-Associated APOE Locus and its Implication in Alzheimer’s Disease and Aging

Gene networks and systems biology in Alzheimer's disease: Insights from multi‐omics approaches

DegCre: Probabilistic association of differential gene expression with regulatory regions

Contact Info

Product

Resources

About