Pervasive RNA-binding protein enrichment on TAD boundaries regulates TAD organization DOI Creative Commons
Qiang Sun, Qin Zhou, Yulong Qiao

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(1)

Published: Dec. 12, 2024

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA-binding proteins (RBPs) in organization. By integrated analyses global RBP binding 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary-associated (baRBPs). We found that baRBP correlated with enhanced insulation strength a CTCF-independent manner. Moreover, associated nascent promoter transcription. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes mild reorganization. conserved phenomenon C2C12 myoblast (MB) cells. downregulated its bound are remodeled during MB differentiation into myotubes. Finally, transcriptional inhibition indeed decreases disrupts boundary insulation. Altogether, findings demonstrate can play an active modulating co-transcriptional association synergistic actions transcripts.

Language: Английский

Review of <i>ABO</i> Expression and Variations based on Transcriptional Regulation of the ABO Blood Group Gene DOI Creative Commons
Kenichi Ogasawara, Rie Sano, Yoshihiko Kominato

et al.

Transfusion Medicine and Hemotherapy, Journal Year: 2024, Volume and Issue: 51(4), P. 210 - 224

Published: Jan. 1, 2024

We review the transcriptional regulation of

Language: Английский

Citations

4
Exploring the roles of RNAs in chromatin architecture using deep learning DOI Creative Commons
Shuzhen Kuang, Katherine S. Pollard

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 29, 2024

Abstract Recent studies have highlighted the impact of both transcription and transcripts on 3D genome organization, particularly its dynamics. Here, we propose a deep learning framework, called AkitaR, that leverages sequences genome-wide RNA-DNA interactions to investigate roles chromatin-associated RNAs (caRNAs) folding in HFFc6 cells. In order disentangle cis - trans -regulatory caRNAs, compared models with nascent transcripts, -located open chromatin data, or DNA sequence alone. Both caRNAs improve models’ predictions, especially at cell-type-specific genomic regions. Analyses feature importance scores reveal contribution TAD boundaries, loops nuclear sub-structures such as speckles nucleoli predictions. Furthermore, identify non-coding (ncRNAs) known regulate structures, MALAT1 NEAT1 , well several new RNAs, RNY5 RPPH1 POLG-DT THBS1-IT1 might modulate architecture through -interactions HFFc6. Our modeling also suggests from Alus other repetitive elements may facilitate R-loop formation. findings provide insights generate testable hypotheses about shaping organization.

Language: Английский

Citations

3
Exploring the Roles of RNAs in Chromatin Architecture Using Deep Learning DOI Creative Commons
Shuzhen Kuang, Katherine S. Pollard

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 24, 2023

Recent studies have highlighted the impact of both transcription and transcripts on 3D genome organization, particularly its dynamics. Here, we propose a deep learning framework, called AkitaR, that leverages sequences genome-wide RNA-DNA interactions to investigate roles chromatin-associated RNAs (caRNAs) folding in HFFc6 cells. In order disentangle

Language: Английский

Citations

3
Pervasive RNA Binding Protein Enrichment on TAD Boundaries Regulates TAD Organization DOI Open Access
Qiang Sun, Qin Zhou, Yulong Qiao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 23, 2023

Abstract Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA binding proteins (RBPs) in organization. By integrated analyses global RBP 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary associated (baRBPs). We also characterize chromatin features baRBP uncover clustering among baRBPs with transcription factors (TFs). Moreover, found that correlated enhanced insulation strength a independent manner. Further revealed nascent promoter thus RBP/transcription may synergistically demarcate TADs. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes remarkable reorganization loss. conserved phenomenon C2C12 myoblast (MB) cells. down-regulated its bound are remodeled during MB differentiation into myotubes (MTs). Knockout Rbfox2 MBs significant reorganization. Finally, transcriptional inhibition indeed decreases disrupts insulation. Altogether, findings demonstrate can play active modulating co-transcriptional association synergistic action transcripts.

Language: Английский

Citations

2
Pervasive RNA Binding Protein Enrichment on TAD Boundaries Regulates TAD Organization DOI Creative Commons
Huating Wang, Qiang Sun, Qin Zhou

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Abstract Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA binding proteins (RBPs) in organization. By integrated analyses global RBP 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary associated (baRBPs). We also characterize chromatin features baRBP uncover clustering among baRBPs with transcription factors (TFs). Moreover, found that correlated enhanced insulation strength a independent manner. Further revealed nascent promoter thus RBP/transcription may synergistically demarcate TADs. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes remarkable reorganization loss. conserved phenomenon C2C12 myoblast (MB) cells. down-regulated its bound are remodeled during MB differentiation into myotubes (MTs). Knockout Rbfox2 MBs significant reorganization. Finally, transcriptional inhibition indeed decreases disrupts insulation. Altogether, findings demonstrate can play active modulating co-transcriptional association synergistic action transcripts.

Language: Английский

Citations

0
Inter3D: Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription DOI Creative Commons
Tianyi Ding, Shaliu Fu, Xiaoyu Zhang

et al.

Genomics Proteomics & Bioinformatics, Journal Year: 2024, Volume and Issue: 22(3)

Published: May 8, 2024

Abstract Topologically associating domain (TAD) reorganization commonly occurs in the cell nucleus and contributes to gene activation inhibition through separation or fusion of adjacent TADs. However, functional genes impacted by TAD alteration underlying mechanism regulating transcription remain be fully elucidated. Here, we first developed a novel approach termed Inter3D specifically identify regulated reorganization. Our study revealed that segregation TADs led disruption intrachromosomal looping at myosin light chain 12B (MYL12B) locus, via meticulous mediating epigenomic landscapes within tumor cells, thereby exhibiting significant correlation with down-regulation its transcriptional activity. Conversely, facilitated interactions, suggesting potential association cytochrome P450 family 27 subfamily B member 1 (CYP27B1). provides comprehensive insight into capture rearrangement-mediated loci moves toward understanding role transcription. The pipeline this is freely available https://github.com/bm2-lab/inter3D https://ngdc.cncb.ac.cn/biocode/tool/BT7399.

Language: Английский

Citations

0
Pervasive RNA-binding protein enrichment on TAD boundaries regulates TAD organization DOI Creative Commons
Qiang Sun, Qin Zhou, Yulong Qiao

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 53(1)

Published: Dec. 12, 2024

Mammalian genome is hierarchically organized by CTCF and cohesin through loop extrusion mechanism to facilitate the organization of topologically associating domains (TADs). Mounting evidence suggests additional factors/mechanisms exist orchestrate TAD formation maintenance. In this study, we investigate potential role RNA-binding proteins (RBPs) in organization. By integrated analyses global RBP binding 3D mapping profiles from both K562 HepG2 cells, our study unveils prevalent enrichment RBPs on boundaries define boundary-associated (baRBPs). We found that baRBP correlated with enhanced insulation strength a CTCF-independent manner. Moreover, associated nascent promoter transcription. Additional experimental testing was performed using RBFox2 as paradigm. Knockdown cells causes mild reorganization. conserved phenomenon C2C12 myoblast (MB) cells. downregulated its bound are remodeled during MB differentiation into myotubes. Finally, transcriptional inhibition indeed decreases disrupts boundary insulation. Altogether, findings demonstrate can play an active modulating co-transcriptional association synergistic actions transcripts.

Language: Английский

Citations

0