Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

Leo, Laura; Romano, Nunzia Colonna

doi:10.3390/ijms22168809

Cited by 7 publications

(4 citation statements)

References 163 publications

(193 reference statements)

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“…The classical method is based on formaldehyde fixation of protein-DNA complexes, however, it suffers from low sensitivity, high background noise, and low precision ( Waldminghaus and Skarstad, 2010 ; Chen et al, 2012 ). A plethora of methods such as Native ChIP, ChIP-Exo, CUT&RUN, CUT&TAG, etc., were developed to overcome these limitations ( Ma et al, 2019 ; Leo and Romano, 2021 ). For topoisomerases, which naturally form covalent adducts with DNA during the catalytic cycle, using specific poisons or mutations, intermediate complexes can be stabilized and enriched without the crosslinking agent ( McKie et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Single-nucleotide resolution detection of Topo IV cleavage activity in the Escherichia coli genome with Topo-Seq

et al. 2023

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Topoisomerase IV (Topo IV) is the main decatenation enzyme in Escherichia coli; it removes catenation links that are formed during DNA replication. Topo IV binding and cleavage sites were previously identified in the E. coli genome with ChIP-Seq and NorfIP. Here, we used a more sensitive, single-nucleotide resolution Topo-Seq procedure to identify Topo IV cleavage sites (TCSs) genome-wide. We detected thousands of TCSs scattered in the bacterial genome. The determined cleavage motif of Topo IV contained previously known cleavage determinants (−4G/+8C, −2A/+6 T, −1 T/+5A) and additional, not observed previously, positions −7C/+11G and −6C/+10G. TCSs were depleted in the Ter macrodomain except for two exceptionally strong non-canonical cleavage sites located in 33 and 38 bp from the XerC-box of the dif-site. Topo IV cleavage activity was increased in Left and Right macrodomains flanking the Ter macrodomain and was especially high in the 50–60 kb region containing the oriC origin of replication. Topo IV enrichment was also increased downstream of highly active transcription units, indicating that the enzyme is involved in relaxation of transcription-induced positive supercoiling.

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Section: Discussionmentioning

confidence: 99%

Single-nucleotide resolution detection of Topo IV cleavage activity in the Escherichia coli genome with Topo-Seq

et al. 2023

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“…Currently, the potential for adding multiple additional omics layers to copy number, gene expression and methylation is rapidly expanding such as chromatin accessibility (using ATAC-seq), epigenetic status (using ChIP or CUT&RUN/TAG for chromatin marks) and proteomics [175]. Moreover, single cell technologies are rapidly evolving and offering further opportunities for deep data mining approaches towards more powerful detection of tumor dependencies.…”

Section: Future Perspectives To Mine Cnas For Novel Candidates and De...mentioning

confidence: 99%

From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma

Decaesteker

Durinck

Roy

et al. 2021

JPM

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Neuroblastoma is a pediatric tumor arising from the sympatho-adrenal lineage and a worldwide leading cause of childhood cancer-related deaths. About half of high-risk patients die from the disease while survivors suffer from multiple therapy-related side-effects. While neuroblastomas present with a low mutational burden, focal and large segmental DNA copy number aberrations are highly recurrent and associated with poor survival. It can be assumed that the affected chromosomal regions contain critical genes implicated in neuroblastoma biology and behavior. More specifically, evidence has emerged that several of these genes are implicated in tumor dependencies thus potentially providing novel therapeutic entry points. In this review, we briefly review the current status of recurrent DNA copy number aberrations in neuroblastoma and provide an overview of the genes affected by these genomic variants for which a direct role in neuroblastoma has been established. Several of these genes are implicated in networks that positively regulate MYCN expression or stability as well as cell cycle control and apoptosis. Finally, we summarize alternative approaches to identify and prioritize candidate copy-number driven dependency genes for neuroblastoma offering novel therapeutic opportunities.

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“…The genetics of AD supports a dichotomous model based on the age when symptoms first appear, which is generally accepted as 65 years old [5]. The highly penetrant mutations in the genes coding for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are considered responsible for an earlier onset (early-onset, EOAD) or familial form, accounting for 5 to 10% of AD cases according to different estimates [6].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease

Bryzgalov

Korbolina

Merkulova

2023

IJMS

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Alzheimer’s disease (AD) is a prevalent type of dementia in elderly populations with a significant genetic component. The accumulating evidence suggests that AD involves a reconfiguration of the epigenetic landscape, including DNA methylation, post-translational modification of histone proteins, and chromatin remodeling. Along with environmental factors, individual specific genetic features play a considerable role in the formation of epigenetic architecture. In this study, we attempt to identify the non-coding regulatory SNPs (rSNPs) able to affect the epigenetic mechanisms in AD. To this end, the multi-omics approach is used. The GEO (Gene Expression Omnibus) available data (GSE153875) for AD patients and controls are integrated to reveal the rSNPs that display allele-specific features in both ChIP-seq profiles of four histone modifications and RNA-seq. Furthermore, we analyze the presence of rSNPs in the promoters of genes reported to be differentially expressed between AD and the normal brain (AD-related genes) and involved in epigenetic regulation according to the EpiFactors database. We also searched for the rSNPs in the promoters of the genes coding for transcription regulators of the identified AD-related genes. These regulators were selected based on the corresponding ChIP-seq peaks (ENCODE) in the promoter regions of these genes. Finally, we formed a panel of rSNPs localized to the promoters of genes that contribute to the epigenetic landscape in AD and, thus, to the genetic predisposition for this disease.

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Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease

Cited by 7 publications

References 163 publications

Single-nucleotide resolution detection of Topo IV cleavage activity in the Escherichia coli genome with Topo-Seq

Single-nucleotide resolution detection of Topo IV cleavage activity in the Escherichia coli genome with Topo-Seq

From DNA Copy Number Gains and Tumor Dependencies to Novel Therapeutic Targets for High-Risk Neuroblastoma

Exploring the Genetic Predisposition to Epigenetic Changes in Alzheimer’s Disease

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