Nucleic Acids Research最新文献_第6页

A dynamic structural unit of phase-separated heterochromatin protein 1α as revealed by integrative structural analyses

IF 14.9 2区生物学

Nucleic Acids Research Pub Date : 2025-03-24 DOI: 10.1093/nar/gkaf154

Ayako Furukawa, Kento Yonezawa, Tatsuki Negami, Yuriko Yoshimura, Aki Hayashi, Jun-ichi Nakayama, Naruhiko Adachi, Toshiya Senda, Kentaro Shimizu, Tohru Terada, Nobutaka Shimizu, Yoshifumi Nishimura

{"title":"A dynamic structural unit of phase-separated heterochromatin protein 1α as revealed by integrative structural analyses","authors":"Ayako Furukawa, Kento Yonezawa, Tatsuki Negami, Yuriko Yoshimura, Aki Hayashi, Jun-ichi Nakayama, Naruhiko Adachi, Toshiya Senda, Kentaro Shimizu, Tohru Terada, Nobutaka Shimizu, Yoshifumi Nishimura","doi":"10.1093/nar/gkaf154","DOIUrl":"https://doi.org/10.1093/nar/gkaf154","url":null,"abstract":"The heterochromatin protein HP1α consists of an N-terminal disordered tail (N-tail), chromodomain (CD), hinge region (HR), and C-terminal chromo shadow domain (CSD). While CD binds to the lysine9-trimethylated histone H3 (H3K9me3) tail in nucleosomes, CSD forms a dimer bridging two nucleosomes with H3K9me3. Phosphorylation of serine residues in the N-tail enhances both H3K9me3 binding and liquid–liquid phase separation (LLPS) by HP1α. We have used integrative structural methods, including nuclear magnetic resonance, small-angle X-ray scattering (SAXS), and multi-angle-light scattering combined with size-exclusion chromatography, and coarse-grained molecular dynamics simulation with SAXS, to probe the HP1α dimer and its CSD deletion monomer. We show that dynamic intra- and intermolecular interactions between the N-tails and basic segments in CD and HR depend on N-tail phosphorylation. While the phosphorylated HP1α dimer undergoes LLPS via the formation of aggregated multimers, the N-tail phosphorylated mutant without CSD still undergoes LLPS, but its structural unit is a dynamic intermolecular dimer formed via the phosphorylated N-tail and a basic segment at the CD end. Furthermore, we reveal that mutation of this basic segment in HP1α affects the size of heterochromatin foci in cultured mammalian cells, suggesting that this interaction plays an important role in heterochromatin formation in vivo.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"57 1","pages":""},"PeriodicalIF":14.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to 'Fam170a deficiency causes male infertility by impairing histone-to-protamine exchange during mouse spermiogenesis'.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf237

引用次数: 0

Integrative structural analysis of NF45-NF90 heterodimers reveals architectural rearrangements and oligomerization on binding dsRNA.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf204

Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, Atlanta G Cook

{"title":"Integrative structural analysis of NF45-NF90 heterodimers reveals architectural rearrangements and oligomerization on binding dsRNA.","authors":"Sophie Winterbourne, Uma Jayachandran, Juan Zou, Juri Rappsilber, Sander Granneman, Atlanta G Cook","doi":"10.1093/nar/gkaf204","DOIUrl":"10.1093/nar/gkaf204","url":null,"abstract":"Complexes of nuclear factors 45 and 90 (NF45-NF90) play a multitude of roles in co- and post-transcriptional RNA processing, including regulating adenosine-to-inosine editing, cassette exon and back splicing, and splicing fidelity. NF45-NF90 complexes recognize double-stranded RNA (dsRNA) and, in human cells, primarily interact with Alu inverted repeats (AluIRs) that are commonly inserted into introns and other non-coding RNA regions. Intronic AluIRs of ∼300 bp can regulate splicing outcomes, such as generation of circular RNAs. We examined domain reorganization of NF45-NF90 domains on dsRNAs exceeding 50 bp to gain insight into its RNA recognition properties on longer dsRNAs. Using a combination of phylogenetic analysis, solution methods (including small angle X-ray scattering and quantitative cross-linking mass spectrometry), machine learning, and negative stain electron microscopy, we generated a model of NF45-NF90 complex formation on dsRNA. Our data reveal that different interactions of NF45-NF90 complexes allow these proteins to coat long stretches of dsRNA. This property of the NF45-NF90 complex has important implications for how long, nuclear dsRNAs are recognized in the nucleus and how this might promote (co)-regulation of specific RNA splicing and editing events that shape the mammalian transcriptome.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Template-independent enzymatic functionalization of DNA oligonucleotides with environment-sensitive nucleotide probes using terminal deoxynucleotidyl transferase.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf108

Pulak Ghosh, Apeksha A Phadte, Bindu Bhojappa, Saravanan Palani, Seergazhi G Srivatsan

{"title":"Template-independent enzymatic functionalization of DNA oligonucleotides with environment-sensitive nucleotide probes using terminal deoxynucleotidyl transferase.","authors":"Pulak Ghosh, Apeksha A Phadte, Bindu Bhojappa, Saravanan Palani, Seergazhi G Srivatsan","doi":"10.1093/nar/gkaf108","DOIUrl":"10.1093/nar/gkaf108","url":null,"abstract":"Given the emerging use of terminal deoxynucleotidyl transferase (TdT) in biotechnology and its clinical potential as a cancer marker and target, the development of a versatile probe system to study its processivity, substrate properties, and inhibition is highly desired. Here, we demonstrate a multilayered application of a series of environment-sensitive fluorescent 2'-deoxynucleotide probes that harness the activity of TdT in accessing site-specifically functionalized DNA oligonucleotides and devising a real-time fluorescence platform to monitor the enzyme activity and identify potential inhibitors. The nucleotides constructed by coupling heterocycles of progressively increasing chemical modifications (selenophene, benzothiophene, benzofuran, and fluorobenzofuran) at the C5 position of 2'-deoxyuridine serve as suitable substrates for TdT, albeit differences in incorporation efficiency. A battery of experiments provided valuable insights into the scope of this functionalization method. It revealed how a fine balance between steric hindrance and stacking interaction between the heterocycle moiety and primer 3'-end nucleobase in the active site modulates the recognition and processing of nucleotides based on their size. Remarkably, the excellent responsiveness of benzofuran-modified dUTP enabled the design of fluorescence assays to estimate TdT activity, and detect nucleotide and non-nucleotide inhibitors. The findings obtained using our probes should significantly advance TdT-based functionalization, diagnostic, and therapeutic strategies.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11963764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A mediator-free sonogenetic switch for therapeutic protein expression in mammalian cells.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf191

Jinbo Huang, Shuai Xue, Ana Palma Teixeira, Martin Fussenegger

{"title":"A mediator-free sonogenetic switch for therapeutic protein expression in mammalian cells.","authors":"Jinbo Huang, Shuai Xue, Ana Palma Teixeira, Martin Fussenegger","doi":"10.1093/nar/gkaf191","DOIUrl":"10.1093/nar/gkaf191","url":null,"abstract":"An ultrasound-responsive transgene circuit can provide non-invasive, spatiotemporally precise remote control of gene expression and cellular behavior in synthetic biology applications. However, current ultrasound-based systems often rely on nanoparticles or harness ultrasound's thermal effects, posing risks of tissue damage and cellular stress that limit their therapeutic potential. Here, we present Spatiotemporal Ultrasound-induced Protein Expression Regulator (SUPER), a novel gene switch enabling mediator-free, non-invasive and direct regulation of protein expression via ultrasound in mammalian cells. SUPER leverages the mammalian reactive oxygen species (ROS) sensing system, featuring KEAP1 (Kelch-like ECH-associated protein 1), NRF2 (nuclear factor erythroid 2-related factor 2), and antioxidant response element (ARE) as its core components. We demonstrate that low-intensity (1.5 W/cm2, ∼45 kHz), brief (40 s) ultrasound exposure generates non-toxic levels of ROS, activating the KEAP1/NRF2 pathway in engineered cells and leading to the controlled expression of target gene(s) via a synthetic ARE promoter. The system exhibits robust expression dynamics, excellent reversibility, and functionality in various cell types, including human mesenchymal stem cell-derived lines (hMSC-TERT). In a proof-of-concept study, ultrasound stimulation of subcutaneously implanted microencapsulated engineered cells stably expressing the sonogenetic circuit in a type 1 diabetic mouse model triggered sufficient insulin production to restore normoglycemia. Our work highlights ultrasound's potential as a precise and non-invasive tool for advancing cell and gene therapies in personalized medicine.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SMARCA4 regulates inducible BRD4 genomic redistribution coupling intrinsic immunity and plasticity in epithelial injury-repair.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf211

Xiaofang Xu, Allan R Brasier

{"title":"SMARCA4 regulates inducible BRD4 genomic redistribution coupling intrinsic immunity and plasticity in epithelial injury-repair.","authors":"Xiaofang Xu, Allan R Brasier","doi":"10.1093/nar/gkaf211","DOIUrl":"10.1093/nar/gkaf211","url":null,"abstract":"Coordinated expression of differentiation and innate pathways is essential for successful mucosal injury-repair. Previously, we discovered that the core SWI/SNF complex ATPase, SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)/Brg1, maintains tumor protein 63 + basal progenitor cells in an epithelial-committed state. In response to viral injury, SMARCA4 complexes BRD4 to activate innate inflammation and promote mesenchymal transition/plasticity. To investigate how innate inflammation couples with plasticity, Cleavage Under Targets and Release Using Nuclease of BRD4 binding was applied to wild type and SMARCA4 knockdown (KD) in mock- or respiratory syncytial virus (RSV)-infected basal cells. In mock-infected cells, BRD4 binds 4017 high-confidence peaks within gene bodies controlling mesenchymal transition pathways. By contrast, RSV replication repositions 2339 BRD4 peaks to open chromatin regions upstream of the genes controlling inducible cytokine, cell adherence, and antiviral programs. Also, we note RSV redistributes BRD4 into super enhancers regulating immune response-associated long noncoding (lnc)RNAs. In SMARCA4 KD cells, BRD4 distribution is reduced on 739 peaks after RSV infection. The boundaries of nucleosome-free regions are reduced by SMARCA4 KD, suggesting its role in maintaining open chromatin of super enhancers. Specifically, SMARCA4-BRD4 enhancer controls lncRNAs important in interferon response factor 1 autoregulation. These data indicate how SWI/SNF ATPases couple BRD4 to lncRNA expression controlling cell state and intrinsic immunity in epithelial injury-repair.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spuriously transcribed RNAs from CRISPR-sgRNA expression plasmids scaffold biomolecular condensate formation and hamper accurate genomic imaging.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf192

Shiqi Mao, Ruonan Wu, Weibang Luo, Jinshan Qin, Antony K Chen

{"title":"Spuriously transcribed RNAs from CRISPR-sgRNA expression plasmids scaffold biomolecular condensate formation and hamper accurate genomic imaging.","authors":"Shiqi Mao, Ruonan Wu, Weibang Luo, Jinshan Qin, Antony K Chen","doi":"10.1093/nar/gkaf192","DOIUrl":"10.1093/nar/gkaf192","url":null,"abstract":"Clustered regularly interspaced short palindromic repeats (CRISPR)-based imaging tools that utilize fluorescently tagged single-guide RNAs (sgRNAs) have enabled versatile analysis of the dynamics of single genomic loci, but the accuracy may be hindered by nonspecific subnuclear probe accumulation, generating false-positive foci in cell nuclei. By examining the subcellular localizations of sgRNA expression plasmids, their RNA transcripts, and several RNA-binding proteins, we found that spuriously transcribed (cryptic) transcripts, produced by sgRNA expression plasmids, are the major contributors of false-positive signals, independent of sgRNA scaffold design or effector probe (i.e. RNA aptamer- or oligonucleotide-based probes) used. These transcripts interact with the paraspeckle core proteins, but not with the sgRNA expression plasmids or the paraspeckle RNA scaffold NEAT1_2, to form nuclear bodies that display liquid-like properties including sphericality, fusion competence, and sensitivity to 1,6-hexanediol. Transfecting sgRNA transcription units (i.e. sgRNA expression cassettes), lacking the plasmid backbones, reduces false-positive signals and enhances genomic imaging accuracy. Overall, this study unveils previously undescribed activities of cryptic plasmid transcripts and presents an easy-to-adapt strategy that can potentially improve the precision of CRISPR-based imaging systems that implement fluorescently tagged sgRNAs.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Formation of multiple G-quadruplexes contributes toward BCR fragility associated with chronic myelogenous leukemia.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf167

Shivangi Sharma, Elizabeth Thomas, Sumedha Dahal, Sayak Das, Shefali Kothari, Urbi Roy, Nitu Kumari, Vidya Gopalakrishnan, Sathees C Raghavan

{"title":"Formation of multiple G-quadruplexes contributes toward BCR fragility associated with chronic myelogenous leukemia.","authors":"Shivangi Sharma, Elizabeth Thomas, Sumedha Dahal, Sayak Das, Shefali Kothari, Urbi Roy, Nitu Kumari, Vidya Gopalakrishnan, Sathees C Raghavan","doi":"10.1093/nar/gkaf167","DOIUrl":"10.1093/nar/gkaf167","url":null,"abstract":"The Philadelphia chromosome, the translocation between BCR and ABL genes, is seen in 95% of chronic myeloid leukemia (CML) patients. Although discovered >60 years ago, the molecular mechanism of BCR fragility is unclear. Here, we have identified several G4 DNA motifs at the BCR fragile region of CML patients. Various lines of experimentation revealed that the breakpoint regions could fold into multiple intramolecular G-quadruplex structures. The sodium bisulfite modification assay revealed single strandedness in the fragile region when present on a plasmid and human genome. Circular dichroism spectroscopy revealed the parallel G4 DNA formation, leading to polymerase arrest at the BCR breakpoints. Intracellular recombination assay revealed that DNA breakage at the BCR fragile region could join with the break generated by ISceI endonuclease. Finally, purified AID could bind and deaminate cytosines when present on single-stranded DNA generated due to G4 DNA, both in vitro and inside the cells. Therefore, our results suggest that AID binds to G4 DNA present at the BCR fragile region, resulting in the deamination of cytosines to uracil and induction of DNA breaks in one of the DNA strands, which can later get converted into a double-strand break, leading to t(9;22) chromosomal translocation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A hidden intrinsic ability of bicistronic expression based on a novel translation reinitiation mechanism in yeast.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf220

Yiwen Sun, Ralph Bock, Zhichao Li

{"title":"A hidden intrinsic ability of bicistronic expression based on a novel translation reinitiation mechanism in yeast.","authors":"Yiwen Sun, Ralph Bock, Zhichao Li","doi":"10.1093/nar/gkaf220","DOIUrl":"10.1093/nar/gkaf220","url":null,"abstract":"Gene organization in operons and co-expression as polycistronic transcripts is characteristic of prokaryotes. With the evolution of the eukaryotic translation machinery, operon structure and expression of polycistrons were largely abandoned. Whether eukaryotes still possess the ability to express polycistrons, and how they functionally activate bacterial operons acquired by horizontal DNA transfer is unknown. Here, we demonstrate that a polycistron can be rapidly activated in yeast by induction of bicistronic expression under selection. We show that induced translation of the downstream cistron in a bicistronic transcript is based on a novel type of reinitiation mediated by the 80S ribosome and triggered by inefficient stop codon recognition, and that induced bicistronic expression is stable and independent of cis-elements. These results provide key insights into the epigenetic mechanism of the pathway of activation. We also developed a yeast strain that efficiently expresses bicistronic constructs, but does not carry any genomic DNA sequence change, and utilized this strain to synthesize a high-value metabolite from a bicistronic expression construct. Together, our results reveal the capacity of yeast to express bicistrons in a previously unrecognized pathway. While this capacity is normally hidden, it can be rapidly induced by selection to improve fitness.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic regions occupied by both RARα and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.

IF 16.6 2区生物学

Nucleic Acids Research Pub Date : 2025-03-20 DOI: 10.1093/nar/gkaf230

Hamidreza Mianesaz, Loránd Göczi, Gergely Nagy, Szilárd Póliska, Lina Fadel, Dóra Bojcsuk, András Penyige, Krisztina Szirák, Farah AlHaman, László Nagy, György Vámosi, Lajos Széles

{"title":"Genomic regions occupied by both RARα and VDR are involved in the convergence and cooperation of retinoid and vitamin D signaling pathways.","authors":"Hamidreza Mianesaz, Loránd Göczi, Gergely Nagy, Szilárd Póliska, Lina Fadel, Dóra Bojcsuk, András Penyige, Krisztina Szirák, Farah AlHaman, László Nagy, György Vámosi, Lajos Széles","doi":"10.1093/nar/gkaf230","DOIUrl":"10.1093/nar/gkaf230","url":null,"abstract":"Retinoic acid receptors (RARs) and the vitamin D receptor (VDR) regulate distinct but overlapping gene sets in multiple cell types. The abundance and characteristics of regulatory regions, occupied by both RARs and VDR are largely unexplored. We used global approaches (ChIP-seq, RNA-seq, and ATAC-seq) and bioinformatics tools to map and characterize common binding regions of RARα and VDR in differentiated human THP-1 cells. We found that the cistromes of ligand-activated RARα and VDR largely overlapped, and their agonists (AM580 and calcitriol) co-regulated several genes, often cooperatively. Common binding regions were frequently (but not exclusively) annotated with co-regulated genes and exhibited increased MED1 occupancy upon ligand stimulation, suggesting their involvement in gene regulation. Chromatin accessibility was typically higher in the common regions than in regions occupied exclusively by RARα or VDR. DNA response elements for RARα (DR1/2/5) and VDR (DR3) were enriched in the common regions, albeit the co-occurrence of the two types of canonical motifs was low (8.4%), suggesting that \"degenerate\" DR1/2/5 and DR3 motifs or other sequences could mediate the binding. In summary, common binding regions of RARα and VDR are at the crossroads of the retinoid and vitamin D pathways, playing important roles in their convergence and cooperation.","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 6","pages":""},"PeriodicalIF":16.6,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0