Integration of multi‐omics layers empowers precision diagnosis through unveiling pathogenic mechanisms on maple syrup urine disease DOI Creative Commons
Juan Ramón Tejedor, Alejandro Soriano‐Sexto, Leonardo Beccari

et al.

Journal of Inherited Metabolic Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Maple syrup urine disease (MSUD) is a rare inherited metabolic disorder characterized by deficient activity of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex, required to metabolize amino acids leucine, isoleucine, and valine. Despite its profound implications, molecular alterations underlying this impairment had not yet been completely elucidated. We performed comprehensive multi-omics integration analysis, including genomic, epigenomic, transcriptomic data from fibroblasts derived cohort MSUD patients unaffected controls genetically characterize an case unravel pathophysiology. exhibit defined episignature that reshapes global DNA methylation landscape, resulting in stimulation HOX cluster genes restriction cell cycle gene-related signatures. Subsequent revealed impact AP1-related CEBPB transcription factors on observed reorganization, with MEIS1 emerging as potential downstream candidate affected robust epigenetic repression patients. Furthermore, layers facilitated identification strong DBT promoter patient wherein no BCKDH pathogenic variants detected. A Circular Chromatin Conformation Capture assay indicated disturbance interactions promoter, thereby unveiling alternative modes inheritance. Integration unveiled networks rewired represents powerful approach diagnostic for genetic disorders unknown bases.

Language: Английский

Factors that determine cell type–specific CTCF binding in health and disease DOI
Catherine Do, Jane A. Skok

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 88, P. 102244 - 102244

Published: Aug. 14, 2024

Language: Английский

Citations

5
DNA methylation shapes the Polycomb landscape during the exit from naive pluripotency DOI
Julien Richard Albert, Teresa Urli, Ana Monteagudo

et al.

Nature Structural & Molecular Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Language: Английский

Citations

4
Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions DOI Creative Commons
Karen Campos-León, Jack Ferguson, Thomas Günther

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012506 - e1012506

Published: Jan. 27, 2025

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes the cell’s transcriptome are thought contribute carcinogenesis. Here, we show by RNA-sequencing oncogenic HPV18 episome replication in primary foreskin keratinocytes (HFKs) drives transcriptional consistent between multiple HFK donors. We have previously shown recruits protein CTCF viral episomes control differentiation-dependent programme. Since important regulator transcription via coordination epigenetic boundaries long-range chromosomal interactions, hypothesised may also manipulate reprogramming. Analysis binding genome ChIP-Seq revealed while total number sites not altered virus, there sub-set either enriched or depleted CTCF. Many these clustered within regulatory elements differentially expressed genes, including tumour suppressor adhesion molecule 1 ( CADM1 ), which supresses epithelial growth invasion. establishment results reduced at promoter upstream enhancer. Loss coincident with repression CADM1, absence CpG hypermethylation, adjacent genes ZBTB16 activated. These data indicate locus subject topological rearrangement following establishment. tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) causes loss interactions start site promoter-enhancer drive reprogramming HPV-induced disease progression.

Language: Английский

Citations

0
Data Readout Techniques for DNA‐Based Information Storage DOI Open Access

B. Liu,

Fei Wang, Chunhai Fan

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

DNA is a natural chemical substrate that carries genetic information, which also serves as powerful toolkit for storing digital data. Compared to traditional storage media, molecules offer higher density, longer lifespan, and lower maintenance energy consumption. In process, data readout critical step bridges the gap between molecular/structures with stored information. With continued development of strategies in technology, techniques have evolved. However, there lack systematic introduction discussion on reported systems, especially correlation design system corresponding selection techniques. This review first introduces two main categories units (i.e., sequence structure) their sequencing nonsequencing methods), then reviewed representative examples notable advancements focusing unit design, technique selection. It emerging approaches assist techniques, such implementation microfluidic fluorescent probes. Finally, paper discusses limitations, challenges, potential approaches.

Language: Английский

Citations

0
Comprehensive metabolomic and epigenomic characterization of microsatellite stable BRAF-mutated colorectal cancer DOI Creative Commons
Aurora Taira, Mervi Aavikko, Riku Katainen

et al.

Oncogene, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Oncogenic codon V600E mutations of the BRAF gene affect 10–15% colorectal cancers, resulting in activation MAPK/ERK signaling pathway and increased cell proliferation survival. BRAF- mutated tumors are often microsatellite unstable characterized by high DNA methylation levels. However, mechanistic link between hypermethylation remains controversial. Understanding this link, particularly stable is great interest as these show poor We metabolomic, epigenetic transcriptomic patterns altogether 39 cancers. Metabolomic analysis tumor tissue showed low levels vitamin C its metabolites tumors. Gene expression indicated dysregulation antioxidant activity lesions. As an important cofactor for TET demethylase enzymes, could directly contribute to decreasing enzymatic activity. Vitamin transporter SLC23A1 expression, well metabolite levels, were inversely correlated with This work proposes a new hypermethylation, inspiring further on role genesis cancer.

Language: Английский

Citations

0
Genome-wide methylome modeling via generative AI incorporating long- and short-range interactions DOI Creative Commons

Fengyao Yan,

Aristeidis G. Telonis, Qin Yang

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(15)

Published: April 11, 2025

Using millions of methylation segments, we developed DiffuCpG, a generative artificial intelligence (AI) diffusion model designed to solve the critical challenge missing data in high-throughput technologies. DiffuCpG goes beyond conventional methods by leveraging both short-range interactions including nearby CpGs from latitude and longitude dataset, local DNA sequences, long-range interactions, three-dimensional genome architecture long-distance correlations, comprehensively methylome. Compared previous methods, through extensive independent validations across different tissue types, cancers, technologies (whole-genome bisulfite sequencing, enhanced reduced representation single-cell arrays), has demonstrated superior performance accuracy, scalability, versatility. On average, sequencing can extend original dataset additional CpGs. As an alternative application AI, addresses key bottleneck epigenetic research will substantially benefit studies relying on data.

Language: Английский

Citations

0
Cell-Type-Specific Transposable Element Demethylation and TAD Remodeling in the Aging Mouse Brain DOI
Qiurui Zeng, Wei Tian,

Amit Klein

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
The phenomenon of genomic imprinting was discovered 40 years ago DOI
Anne C. Ferguson‐Smith, Marisa S. Bartolomei

Nature, Journal Year: 2024, Volume and Issue: 629(8013), P. 763 - 765

Published: May 14, 2024

Language: Английский

Citations

2
The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation DOI Creative Commons
Ana Monteagudo, Julien Richard Albert, Margherita Scarpa

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(18), P. 10934 - 10950

Published: Aug. 23, 2024

Abstract During mammalian embryogenesis, both the 5-cytosine DNA methylation (5meC) landscape and three dimensional (3D) chromatin architecture are profoundly remodeled during a process known as ‘epigenetic reprogramming.’ An understudied aspect of epigenetic reprogramming is how 5meC flux, per se, affects 3D genome. This pertinent given 5meC-sensitivity binding for key regulator chromosome folding: CTCF. We profiled CTCF using mouse embryonic stem cell (ESC) differentiation protocol that models dynamics. Mouse ESCs lacking machinery able to exit naive pluripotency, thus allowing dissection subtle effects on gene expression. performed HiChIP in wild-type mutant conditions assess gained CTCF–CTCF contacts absence 5meC. H3K27ac determine impact ectopic has cis-regulatory contacts. Using epigenome editing, we demonstrated methyl-mark impair at select loci. Finally, detailed imprinted Zdbf2 locus showed 5meC-antagonism allows proper regulation differentiation. work provides comprehensive overview impacts genome relevant model early events.

Language: Английский

Citations

2
Repetitive Sequence Stability in Embryonic Stem Cells DOI Open Access
Guang Shi,

Qianwen Pang,

Zhancheng Lin

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8819 - 8819

Published: Aug. 13, 2024

Repetitive sequences play an indispensable role in gene expression, transcriptional regulation, and chromosome arrangements through trans cis regulation. In this review, focusing on recent advances, we summarize the epigenetic regulatory mechanisms of repetitive embryonic stem cells. We aim to bridge knowledge gap by discussing DNA damage repair pathway choices summarizing significance chromatin organization response damage. By consolidating these insights, underscore critical relationship between stability early development, seeking provide a deeper understanding sequence setting stage for further research potential therapeutic strategies developmental biology regenerative medicine.

Language: Английский

Citations

1