G-quadruplexes as pivotal components of cis-regulatory elements in the human genome DOI Creative Commons
Rongxin Zhang, Yuqi Wang, Cheng Wang

et al.

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 26, 2024

Cis-regulatory elements (CREs) are crucial for regulating gene expression, and G-quadruplexes (G4s), as prototypal non-canonical DNA structures, may play a role in this regulation. However, the relationship between G4s CREs, especially with non-promoter-like functional elements, requires further systematic investigation. We aimed to investigate associations human cCREs (candidate CREs) inferred from Encyclopedia of Elements (ENCODE) data. found that prominently enriched most types cCREs, those promoter-like signatures (PLS). The co-occurrence CTCF signals H3K4me3 or H3K27ac strengthens association G4s. Genetic variants G4s, particularly within their G-runs, exhibit higher regulatory potential deleterious effects compared cCREs. G-runs near transcriptional start sites (TSSs) more evolutionarily constrained while far TSS relatively less conserved. presence is often linked favorable local chromatin environment activation execution function potentially attributable formation G4 secondary structures. Finally, we discovered G4-associated widespread variety cancers. Our study suggests integral components cis-regulatory extending beyond promoters. primary sequences associated localization structures these elements. Therefore, propose defining pivotal genome.

Language: Английский

PTMoreR-enabled cross-species PTM mapping and comparative phosphoproteomics across mammals DOI Creative Commons
Shisheng Wang, Yi Di, Yin Yang

et al.

Cell Reports Methods, Journal Year: 2024, Volume and Issue: 4(9), P. 100859 - 100859

Published: Sept. 1, 2024

Language: Английский

Citations

3
Functional associations of evolutionarily recent human genes exhibit sensitivity to the 3D genome landscape and disease DOI Creative Commons

Katherine Fleck,

Victor Luria,

Nitanta Garag

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 17, 2024

Summary Genome organization is intricately tied to regulating genes and associated cell fate decisions. Here, we examine the positioning functional significance of human genes, grouped by their lineage restriction level, within 3D genome. We reveal that different levels have distinct relationships with both domains loop anchors, remarkably consistent boundaries across types. While associations each group are primarily type-specific, conserved maintain greater stability genomic features disease than recently evolved genes. Furthermore, expression these various tissues follows an evolutionary progression, such RNA increase from young restricted ancient present in most species. Thus, gene age, function, contribute tissue-specific regulation development disease.

Language: Английский

Citations

2
Analysis of live cell data with G-DNABERT supports a role for G-quadruplexes in chromatin looping DOI Creative Commons
Dmitry A. Konovalov, Dmitriy Umerenkov, Alan Herbert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Alternative DNA conformation formed by sequences called flipons potentially alter the readout of genetic information directing shape-specific assembly complexes on The biological roles G-quadruplexes motifs rich in guanosine repeats have been investigated experimentally using many different methodologies including G4-seq, G4 ChIP-seq, permanganate nuclease footprinting (KEx), KAS-seq, CUT&Tag with varying degrees overlap between results. Here we trained large language model DNABERT existing data generated KEx, a rapid chemical technique performed live, intact cells potassium permanganate. snapshot flipon state when combined results from other vitro methods that are permeabilized cells, allows high confidence mapping G-flipons to proximal enhancer and promoter sequences. Using G4-DNABERT predictions,with ENdb, Zoonomia cCREs single cell experiments, found support for where G4-quadruplexes regulate gene expression through chromatin loop formation.

Language: Английский

Citations

2
Systematic single-cell analysis reveals dynamic control of transposable element activity orchestrating the endothelial-to-hematopoietic transition DOI Creative Commons
Cong Feng,

Ruxiu Tie,

Saige Xin

et al.

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 27, 2024

Abstract Background The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little known about how TEs contribute to the human mouse. Results We reconstructed single-cell trajectories mouse resolved dynamic patterns EHT. Most presented a transient co-upregulation pattern along trajectories, coinciding with temporal relaxation epigenetic silencing systems. TE products can be sensed multiple recognition receptors, triggering signaling facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched cells higher expression. Furthermore, constructed cis-regulatory network accessible identified potential TE-derived enhancers boost specific marker genes. Conclusions Our study provides systematic vision are dynamically controlled fate decisions through transcriptional networks, pre-train immunity nascent HSCs.

Language: Английский

Citations

2
G-quadruplexes as pivotal components of cis-regulatory elements in the human genome DOI Creative Commons
Rongxin Zhang, Yuqi Wang, Cheng Wang

et al.

BMC Biology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 26, 2024

Cis-regulatory elements (CREs) are crucial for regulating gene expression, and G-quadruplexes (G4s), as prototypal non-canonical DNA structures, may play a role in this regulation. However, the relationship between G4s CREs, especially with non-promoter-like functional elements, requires further systematic investigation. We aimed to investigate associations human cCREs (candidate CREs) inferred from Encyclopedia of Elements (ENCODE) data. found that prominently enriched most types cCREs, those promoter-like signatures (PLS). The co-occurrence CTCF signals H3K4me3 or H3K27ac strengthens association G4s. Genetic variants G4s, particularly within their G-runs, exhibit higher regulatory potential deleterious effects compared cCREs. G-runs near transcriptional start sites (TSSs) more evolutionarily constrained while far TSS relatively less conserved. presence is often linked favorable local chromatin environment activation execution function potentially attributable formation G4 secondary structures. Finally, we discovered G4-associated widespread variety cancers. Our study suggests integral components cis-regulatory extending beyond promoters. primary sequences associated localization structures these elements. Therefore, propose defining pivotal genome.

Language: Английский

Citations

2