Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes

Schwab, Katjana; Coronel, Luis; Riege, Konstantin; Sacramento, Erika Kelmer; Rahnis, Norman; Häckes, David; Cirri, Emilio; Groth, Marco; Hoffmann, Steve; Fischer, Martin

doi:10.1038/s41420-023-01378-1

Cited by 6 publications

(2 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data used in the analyses of this study were downloaded from NCBI Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/ ). The analyzed datasets include: BG4 ChIP-seq in K562 cells ( GSE107690 ); BG4 ChIP-seq in HepG2 cells ( GSE145090 ); G4P ChIP-seq in A549, H1975 and HEK293T cells ( GSE133379 ); TMPyp4-treated CUT&Tag and TT-seq dataset in HEK293T cells ( GSE178668 ); SG4 ChIP-seq in U2OS and K562 cells 77 ( GSE207567 ); RNA-seq in U2OS 78 ( GSE173483 ), K562 79 ( GSE228464 ), A549 80 ( GSE197555 ) and H1975 81 cells ( GSE193258 ). The ChIP-seq datasets of histone modification marks, chromatin remodelers and TFs, and the RNA-seq datasets of HepG2 and K562 were downloaded from ENCODE (URL: https://www.encodeproject.org/ ), and the dataset names are listed in Supplementary Data 2 .…”

mentioning

confidence: 99%

Integrative genomic analyses of promoter G-quadruplexes reveal their selective constraint and association with gene activation

Wang

et al. 2023

Commun Biol

View full text Add to dashboard Cite

G-quadruplexes (G4s) regulate DNA replication and gene transcription, and are enriched in promoters without fully appreciated functional relevance. Here we show high selection pressure on putative G4 (pG4) forming sequences in promoters through investigating genetic and genomic data. Analyses of 76,156 whole-genome sequences reveal that G-tracts and connecting loops in promoter pG4s display lower or higher allele frequencies, respectively, than pG4-flanking regions, and central guanines (Gs) in G-tracts show higher selection pressure than other Gs. Additionally, pG4-promoters produce over 72.4% of transcripts, and promoter G4-containing genes are expressed at relatively high levels. Most genes repressed by TMPyP4, a G4-ligand, regulate epigenetic processes, and promoter G4s are enriched with gene activation histone marks, chromatin remodeler and transcription factor binding sites. Consistently, cis-expression quantitative trait loci (cis-eQTLs) are enriched in promoter pG4s and their G-tracts. Overall, our study demonstrates selective constraint of promoter G4s and reinforces their stimulative role in gene expression.

show abstract

mentioning

confidence: 99%

Integrative genomic analyses of promoter G-quadruplexes reveal their selective constraint and association with gene activation

Wang

et al. 2023

Commun Biol

View full text Add to dashboard Cite

show abstract

“…2G ). In addition to NRSN2‐AS1 , lncRNAs recurrently up‐regulated by p53 include the RFX7 targets MIR22HG , PDCD4‐AS1 , and TOB1‐AS1 [ 61 ] (Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

The landscape of human p53‐regulated long non‐coding RNAs reveals critical host gene co‐regulation

2023

Self Cite

View full text Add to dashboard Cite

The role of long non-coding RNAs (lncRNAs) in p53-mediated tumor suppression has become increasingly appreciated in the past decade. Thus, the identification of p53-regulated lncRNAs can be a promising starting point to select and prioritize lncRNAs for functional analyses. By integrating transcriptome and transcription factor-binding data, we identified 379 lncRNAs that are recurrently differentially regulated by p53. Dissecting the mechanisms by which p53 regulates many of them, we identified sets of lncRNAs regulated either directly by p53 or indirectly through the p53-RFX7 and p53-p21-DREAM/RB:E2F pathways. Importantly, we identified multiple p53-responsive lncRNAs that are co-regulated with their protein-coding host genes, revealing an important mechanism by which p53 may regulate lncRNAs. Further analysis of transcriptome data and clinical data from cancer patients showed that recurrently p53-regulated lncRNAs are associated with patient survival. Together, the integrative analysis of the landscape of p53-regulated lncRNAs provides a powerful resource facilitating the identification of lncRNA function and displays the mechanisms of p53-dependent regulation that could be exploited for developing anticancer approaches.

show abstract

A variant in long noncoding RNA NORSF affects granulosa cells response to transcription factor RFX7

Wang,

Zhang,

Sheng

et al. 2024

Journal Cellular Physiology

View full text Add to dashboard Cite

NORSF is a nuclear long noncoding RNA (lncRNA) that contributes to the follicular atresia and restrains 17β‐estradiol (E2) release by granulosa cells (GCs). Importantly, it is also a potential candidate gene in the quantitative trait locus (QTLs) for sow fertility traits. We identified NORSF as a candidate (causal) gene affecting sow fertility traits. A novel G–A variant was discovered at −478 nt of the NORSF promoter and termed as g.−478G>A. Association analysis revealed that this variant was associated with sow fertility traits (e.g., the total number of piglets born, the total number of piglets born alive, and the number of healthy piglets). Mechanistically, the g.−478G>A variant reduced the binding activity of the NORSF promoter to its transcription activator regulatory factor X7 (RFX7), leading to decreased NORSF promoter activity and transcription levels in sow GCs (sGCs), and weakened inhibitory effects on the transcription of CYP19A1, which encodes a rate‐limiting enzyme for E2 synthesis and E2 release by sGCs. In addition, RFX7 is transcriptionally activated by P53, which restrains E2 release from sGCs via the RFX7/NORSF/CYP19A1 pathway. These findings indicate that the lncRNA NORSF is a causal gene in QTLs for sow fertility traits and define the P53/NORSF/CYP19A1 pathway as a new signaling pathway affecting sow reproduction, which provides a new target for improving female fertility.

show abstract

Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes

Cited by 6 publications

References 73 publications

Integrative genomic analyses of promoter G-quadruplexes reveal their selective constraint and association with gene activation

Integrative genomic analyses of promoter G-quadruplexes reveal their selective constraint and association with gene activation

The landscape of human p53‐regulated long non‐coding RNAs reveals critical host gene co‐regulation

A variant in long noncoding RNA NORSF affects granulosa cells response to transcription factor RFX7

Contact Info

Product

Resources

About