The acetyltransferase p300 is recruited <i>in trans</i> to multiple enhancer sites by lncSmad7

Maldotti, Mara; Lauria, Andrea; Anselmi, Francesca; Molineris, Ivan; Tamburrini, Annalaura; Meng, Guohua; Polignano, Isabelle Laurence; Scrivano, Mirko Giuseppe; Campestre, Fabiola; Simon, Lisa Marie; Rapelli, Stefania; Morandi, Edoardo; Incarnato, Danny; Oliviero, Salvatore

doi:10.1093/nar/gkac083

Cited by 14 publications

(11 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Actually in vitro biochemical experiments show that even TXP as small as 12 nt can be functional (35), and in a previous work we experimentally validated functional specificity of some short TPXs formed by lncSmad7 (10). Moreover Matveishina et al elaborated a practical guidance in genome-wide RNA:DNA triple helix prediction using experimentally validated binding sites of 4 lncRNA and found that the minimal available cutoff in TPX length of Triplexator produced the best prediction (27).…”

Section: Discussionmentioning

confidence: 86%

“…For example, the murine lncRNA EPR binds on Arrdc3 promoter, thus activating its expression and modulating the epithelial to mesenchymal transition (10). Similarly, LncSmad7 binds and recruits p300 to enhancer regions in trans , triggering their acetylation and transcriptional activation of their target genes, controlling the expression of key stemness regulators (11). Other examples can be found in recent reviews (12,13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RNABSdb and 3plex enable deep computational investigation of triplex forming lncRNAs

Cicconetti

Lauria

Proserpio

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

1.AbstractLong non-coding RNAs (lncRNAs) regulate gene expression through different molecular mechanisms, including DNA binding. We curated a database of RNA Binding Sites (RNABSdb) by harmonising publicly available raw-data of RNA-DNA binding. This resource is required to enable systematic studies on transcriptional regulation driven by lncRNAs. Focusing on high quality experiments, we found that the number of binding sites for each lncRNAs varies from hundreds to tens of thousands. Despite being poorly characterised, the formation of RNA:DNA:DNA triple helices (TPXs) is one of the molecular mechanisms that allow lncRNAs to bind the genome and drive alteration of gene expression. Few computational methods exist which can predict TPXs in silico and, in this study, we developed 3plex, a software that improves the state-of-the-art TPXs prediction method. Leveraging the data collected in RNABSdb for lncRNAs known to form funcional TPXs, we showed that 3plex outperformed existing approaches. Our analysis showed that TPXs tend to be shorter and more degenerated than expected. Finally, we applied 3plex to all the lncRNAs collected in RNABSdb and we show that the majority of lncRNA could bind the genome by TPXs formation.Data and software are available at https://molinerislab.github.io/RNABSdb/.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

RNABSdb and 3plex enable deep computational investigation of triplex forming lncRNAs

Cicconetti

Lauria

Proserpio

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Herein, we discovered that a histone acetyltransferase p300 can be recruited by SIX5, and both EYA3 and p300 are required for the transcription of their target genes. Transcription factors typically recruit p300 to the target gene promoters where p300 acetylates chromatin ( 31 ). Although the specific mechanism by which the EYA3-SIX5-p300 complex regulates gene transcription is unclear, we speculate that these three proteins may play their respective roles.…”

Section: Discussionmentioning

confidence: 99%

Both a hypoxia-inducible EYA3 and a histone acetyltransferase p300 function as coactivators of SIX5 to mediate tumorigenesis and cancer progression

Chao¹,

Liu²

2022

Ann Transl Med

View full text Add to dashboard Cite

Background: The transcription partners of eyes absent homologs and sine oculis homeobox homologs (EYA-SIX) contribute to tumorigenesis and progression of multiple cancers through mediating the expression of oncogenes and tumor suppressors. This study aimed to determine the roles of individual EYA-SIX partners and their downstream targets in colorectal cancer (CRC).Methods: Immunoblot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to measure protein and gene expression levels. Cell Counting Kit-8 (CCK-8) assay, colony formation, cell invasion assays, and a tumor xenograft model were chosen to investigate tumor cell growth.Immunoprecipitation, mass spectrometry, and co-immunoprecipitation (Co-IP) experiments were performed to determine the assembly of the SIX5-associated complex. Chromatin immunoprecipitation (ChIP) assay was used to evaluate the occupancy of SIX5-associated complex on its target gene promoters. Results:We discovered that the hypoxia-induced EYA3 coupled with SIX5 and a histone acetyltransferase p300 to assemble a complex in CRC biopsies. The EYA3-SIX5-p300 complex was required for the transactivation of epidermal growth factor receptor (EGFR), vascular endothelial growth factor D (VEGFD), and five matrix metallopeptidases (MMPs), including MMP3, MMP7, MMP8, MMP21, and MMP26. The results of ChIP revealed that the EYA3-SIX5-p300 complex specifically bound to the promoters of EGFR/ VEGFD/MMPs. Disruption of the assembly of EYA3-SIX5-p300 complex decreased the expression of EGFR/VEGFD/MMPs, inhibiting CRC cell growth. Administration of EYA3 inhibitor (benzarone) in mice harboring tumor xenografts significantly inhibited tumor growth. Conclusions:The hypoxia-dependent EYA3-SIX5-p300 complex is involved in the pathogenesis of CRC through mediating EGFR/VEGFD/MMPs and targeting this complex may represent a new therapeutic strategy for CRC treatment.

show abstract

“…Another emerging type of gene regulation involving lncRNAs requires the formation of RNA:DNA:DNA triple helices through Hogsteen base pairing in cis or in trans [ 11 , 205 ]. Algorithms have been developed to identify putative genomic regions that can form triple helices with a given lncRNA [ 206 , 207 ].…”

Section: The Search For Relevant Lncrnas Using Integrated Approachesmentioning

confidence: 99%

“…Now, the non-coding genome is emerging as a major source of human diversity and has been found to participate in physiological and pathological processes, but its dynamics of expression, mechanisms of action, and functional roles remain poorly characterized [ 7 ]. At the molecular level, the most studied function of lncRNAs is the modulation (induction or repression) of gene expression, which includes the regulation of neighboring genes in cis [ 8 ], the complex formation with RNA binding proteins and chromatin modifiers [ 9 , 10 ], and the binding to specific genomic regions via the triple-helix formation in trans [ 11 ]. Still, they also work at the post-transcriptional level by competing with miRNAs [ 12 ], acting as splicing regulators, or promoting RNA degradation [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders

Liaci

Prandi

Pavinato

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

In the human brain, long non-coding RNAs (lncRNAs) are widely expressed in an exquisitely temporally and spatially regulated manner, thus suggesting their contribution to normal brain development and their probable involvement in the molecular pathology of neurodevelopmental disorders (NDD). Bypassing the classic protein-centric conception of disease mechanisms, some studies have been conducted to identify and characterize the putative roles of non-coding sequences in the genetic pathogenesis and diagnosis of complex diseases. However, their involvement in NDD, and more specifically in intellectual disability (ID), is still poorly documented and only a few genomic alterations affecting the lncRNAs function and/or expression have been causally linked to the disease endophenotype. Considering that a significant fraction of patients still lacks a genetic or molecular explanation, we expect that a deeper investigation of the non-coding genome will unravel novel pathogenic mechanisms, opening new translational opportunities. Here, we present evidence of the possible involvement of many lncRNAs in the etiology of different forms of ID and NDD, grouping the candidate disease-genes in the most frequently affected cellular processes in which ID-risk genes were previously collected. We also illustrate new approaches for the identification and prioritization of NDD-risk lncRNAs, together with the current strategies to exploit them in diagnosis.

show abstract

The acetyltransferase p300 is recruited in trans to multiple enhancer sites by lncSmad7

Cited by 14 publications

References 74 publications

RNABSdb and 3plex enable deep computational investigation of triplex forming lncRNAs

RNABSdb and 3plex enable deep computational investigation of triplex forming lncRNAs

Both a hypoxia-inducible EYA3 and a histone acetyltransferase p300 function as coactivators of SIX5 to mediate tumorigenesis and cancer progression

The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders

Contact Info

Product

Resources

About