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A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region

Pathogenic single-nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving the FOXF1 transcription factor gene or CNV deletions of its distant lung-specific enhancer are responsible for alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a rarely diagnosed...

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Autores principales: Szafranski, Przemyslaw, Stankiewicz, Paweł
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609350/
https://www.ncbi.nlm.nih.gov/pubmed/37888207
http://dx.doi.org/10.3390/ncrna9050061
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author Szafranski, Przemyslaw
Stankiewicz, Paweł
author_facet Szafranski, Przemyslaw
Stankiewicz, Paweł
author_sort Szafranski, Przemyslaw
collection PubMed
description Pathogenic single-nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving the FOXF1 transcription factor gene or CNV deletions of its distant lung-specific enhancer are responsible for alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a rarely diagnosed lethal lung developmental disorder in neonates. In contrast to SNVs within FOXF1 and CNV deletions involving only the FOXF1 enhancer, larger-sized deletions involving FOXF1 and the adjacent, oppositely oriented lncRNA gene FENDRR have additionally been associated with hypoplastic left heart syndrome and single umbilical artery (SUA). Here, in an ACDMPV infant without any congenital heart defect or SUA, we identified a small 5 kb CNV deletion that removed the paternal allele of FOXF1 and its promoter, leaving FENDRR and its promoter intact. Reporter assay in the IMR-90 fetal cell line implied that the deletion may indeed not have significantly affected FENDRR expression. It also showed a polarization of the FOXF1-FENDRR inter-promoter region consisting of its ability to increase the transcription of FENDRR but not FOXF1. Interestingly, this transcription-stimulating activity was suppressed in the presence of the FOXF1 promoter. Our data shed more light on the interactions between neighboring promoters of FOXF1-FENDRR and possibly other divergently transcribed mRNA-lncRNA gene pairs.
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spelling pubmed-106093502023-10-28 A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region Szafranski, Przemyslaw Stankiewicz, Paweł Noncoding RNA Communication Pathogenic single-nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving the FOXF1 transcription factor gene or CNV deletions of its distant lung-specific enhancer are responsible for alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a rarely diagnosed lethal lung developmental disorder in neonates. In contrast to SNVs within FOXF1 and CNV deletions involving only the FOXF1 enhancer, larger-sized deletions involving FOXF1 and the adjacent, oppositely oriented lncRNA gene FENDRR have additionally been associated with hypoplastic left heart syndrome and single umbilical artery (SUA). Here, in an ACDMPV infant without any congenital heart defect or SUA, we identified a small 5 kb CNV deletion that removed the paternal allele of FOXF1 and its promoter, leaving FENDRR and its promoter intact. Reporter assay in the IMR-90 fetal cell line implied that the deletion may indeed not have significantly affected FENDRR expression. It also showed a polarization of the FOXF1-FENDRR inter-promoter region consisting of its ability to increase the transcription of FENDRR but not FOXF1. Interestingly, this transcription-stimulating activity was suppressed in the presence of the FOXF1 promoter. Our data shed more light on the interactions between neighboring promoters of FOXF1-FENDRR and possibly other divergently transcribed mRNA-lncRNA gene pairs. MDPI 2023-10-09 /pmc/articles/PMC10609350/ /pubmed/37888207 http://dx.doi.org/10.3390/ncrna9050061 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Szafranski, Przemyslaw
Stankiewicz, Paweł
A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title_full A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title_fullStr A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title_full_unstemmed A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title_short A Small De Novo CNV Deletion of the Paternal Copy of FOXF1, Leaving lncRNA FENDRR Intact, Provides Insight into Their Bidirectional Promoter Region
title_sort small de novo cnv deletion of the paternal copy of foxf1, leaving lncrna fendrr intact, provides insight into their bidirectional promoter region
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609350/
https://www.ncbi.nlm.nih.gov/pubmed/37888207
http://dx.doi.org/10.3390/ncrna9050061
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