Ligand-Dependent Corepressor (LCoR) Is a Rexinoid-Inhibited Peroxisome Proliferator-Activated Receptor <i>γ</i>–Retinoid X Receptor <i>α</i> Coactivator

Shalom‐Barak, Tali; Liersemann, Jaclyn; Memari, Babak; Flechner, Lawrence; Devor, Caitlin E.; Bernardo, Tiffany M; Kim, Su Yeon; Matsumoto, Nobuyuki; Friedman, Scott L.; Evans, Ronald M.; White, John H.; Barak, Yaacov

doi:10.1128/mcb.00107-17

Cited by 10 publications

(4 citation statements)

References 47 publications

(73 reference statements)

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“…Another interesting candidate is LCOR , which is upregulated in the AF+AVB model and encodes a transcriptional cofactor that interacts with PPARγ and RXRα to control gene expression. 38 While further experiments are needed to determine the extent by which LCOR modifies gene expression in AF+AVB and contributes to the pathology, our RNA-seq experiments detected the dysregulation of 2 of its likely targets based on the literature: CPT1A (see above) and the cell cycle regulator CDKN1A. 39 …”

Section: Discussionmentioning

confidence: 97%

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Leblanc

Hassani

Liesinger

et al. 2021

Circ: Arrhythmia and Electrophysiology

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Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained in subjects with advanced disease, so it is difficult to study earlier-stage pathophysiology in humans. Methods - Here, we characterized comprehensively the transcriptomic (miRNAseq and mRNAseq) changes in the left atria of two robust canine AF-models after one week of electrically-maintained AF, without or with ventricular rate-control via atrioventricular node-ablation/ventricular pacing. Results - Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene-set enrichment analyses highlighted known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular trans-differentiation. Of interest, we found dysregulation of a cluster of non-coding RNAs, including many microRNAs but also the MEG3 long non-coding RNA orthologue, located in the syntenic region of the imprinted human DLK1-DIO3 locus. Interestingly (in the light of other recent observations), our analysis identified gene-targets of differentially expressed microRNAs at the DLK1-DIO3 locus implicating glutamate signaling in AF pathophysiology. Conclusions - Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF in humans.

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Section: Discussionmentioning

confidence: 97%

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Leblanc

Hassani

Liesinger

et al. 2021

Circ: Arrhythmia and Electrophysiology

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“…On the other hand, NFKBIA is an inhibitor of the dimerization of transcription factors p50 and RELA in the canonical pathway [ 20 , 41 ]. Additionally, IFRD2 [ 42 ], LCOR [ 43 , 44 ], LRRC33 [ 45 ], NLK [ 46 ], PGRN [ 47 ], SIGLEC11 [ 48 ], and TRAF1 [ 49 ] have suppressive effects on canonical NFκB signaling. The expression of these genes was significantly upregulated in transitional carriers ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa

et al. 2022

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Foot-and-mouth disease virus (FMDV) can persistently infect pharyngeal epithelia in ruminants but not in pigs. Our previous studies demonstrated that persistent FMDV infection in cattle was associated with under-expression of several chemokines that recruit immune cells. This report focuses on the analysis of differentially expressed genes (DEG) identified during the transitional phase of infection, defined as the period when animals diverge between becoming carriers or terminators. During this phase, Th17-stimulating cytokines (IL6 and IL23A) and Th17-recruiting chemokines (CCL14 and CCL20) were upregulated in animals that were still infected (transitional carriers) compared to those that had recently cleared infection (terminators), whereas chemokines recruiting neutrophils and CD8+ T effector cells (CCL3 and ELR+CXCLs) were downregulated. Upregulated Th17-specific receptor, CCR6, and Th17-associated genes, CD146, MIR155, and ThPOK, suggested increased Th17 cell activity in transitional carriers. However, a complex interplay of the Th17 regulatory axis was indicated by non-significant upregulation of IL17A and downregulation of IL17F, two hallmarks of TH17 activity. Other DEG suggested that transitional carriers had upregulated aryl hydrocarbon receptor (AHR), non-canonical NFκB signaling, and downregulated canonical NFκB signaling. The results described herein provide novel insights into the mechanisms of establishment of FMDV persistence. Additionally, the fact that ruminants, unlike pigs, produce a large amount of AHR ligands suggests a plausible explanation of why FMDV persists in ruminants, but not in pigs.

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“…3B). Another interesting candidate is LCOR, which is up-regulated in the AF+AVB model and encodes a transcriptional cofactor that interacts with PPARγ and RXRα to control gene expression 38 . While further experiments are needed to determine the extent by which LCOR modifies gene expression in AF+AVB and contributes to the pathology, our RNA-seq experiments detected the dysregulation of two of its likely targets based on the literature: CPT1A (see above) and the cell cycle regulator CDKN1A 39 .…”

Section: Molecular Remodeling In Af With Versus Without Avbmentioning

confidence: 99%

Transcriptomic profiling of canine atrial fibrillation models after one week of sustained arrhythmia

Leblanc

Liesinger

et al. 2021

Preprint

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Atrial fibrillation (AF), the most common arrhythmia with an overall prevalence of 0.51%, is associated with increased morbidity and mortality, as well as important healthcare costs. AF develops over many years and is often associated with substantial changes in the structural and electrophysiological properties of the atria. Because AF may lack subclinical symptoms at onset, it has been difficult to study the molecular and cellular events associated with earlier stages of this pathology in humans. Here, we characterized comprehensively the transcriptomic changes that occur in the atria of two robust canine AF models, electrically maintained AF without and with a controlled ventricular rate achieved by radiofrequency-ablation of the atrioventricular node (ventricular pacing), after one week of maintenance. Our RNA-sequencing experiments identified thousands of genes that are differentially expressed, including a majority that have never before been implicated in AF. Gene set enrichment analyses identified known (e.g. extracellular matrix structure organization) but also many novel pathways (e.g. muscle structure development, striated muscle cell differentiation) that may play a role in tissue remodeling and/or cellular trans-differentiation. Of interest, we found dysregulation of a cluster of non-coding ribonucleic acids (RNAs), including many microRNAs but also the MEG3 long non-coding RNA orthologue, located in the syntenic region of the imprinted human DLK1-DIO3 locus. Our results capture molecular events that occur at an early stage of disease development using well-characterized animal models, and may therefore inform future studies that aim to further dissect the causes of AF and factors involved in its progression in humans.

show abstract

Ligand-Dependent Corepressor (LCoR) Is a Rexinoid-Inhibited Peroxisome Proliferator-Activated Receptor γ–Retinoid X Receptor α Coactivator

Cited by 10 publications

References 47 publications

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Transcriptomic Profiling of Canine Atrial Fibrillation Models After One Week of Sustained Arrhythmia

Inferred Causal Mechanisms of Persistent FMDV Infection in Cattle from Differential Gene Expression in the Nasopharyngeal Mucosa

Transcriptomic profiling of canine atrial fibrillation models after one week of sustained arrhythmia

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