Emerging mechanisms of elastin transcriptional regulation

Procknow, Sara S.; Kozel, Beth A.

doi:10.1152/ajpcell.00228.2022

Cited by 6 publications

(3 citation statements)

References 144 publications

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“…Nevertheless, the transcript structure diversity pattern for the majority of genes is consistent across samples where they are expressed at substantial levels. Elastin (ELN), which is an important component of the extracellular matrix 29 , is the gene with the greatest number of detected transcripts in our dataset (283 in total). We find that in most samples, distinct transcripts of ELN are characterized by different ECs (Fig.…”

Section: Sample-specific and Global Changes In Predominantmentioning

confidence: 99%

The ENCODE4 long-read RNA-seq collection reveals distinct classes of transcript structure diversity

Reese

Williams

Balderrama-Gutierrez

et al. 2023

Preprint

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The majority of mammalian genes encode multiple transcript isoforms that result from differential promoter use, changes in exonic splicing, and alternative 3′ end choice. Detecting and quantifying transcript isoforms across tissues, cell types, and species has been extremely challenging because transcripts are much longer than the short reads normally used for RNA-seq. By contrast, long-read RNA-seq (LR-RNA-seq) gives the complete structure of most transcripts. We sequenced 264 LR-RNA-seq PacBio libraries totaling over 1 billion circular consensus reads (CCS) for 81 unique human and mouse samples. We detect at least one full-length transcript from 87.7% of annotated human protein coding genes and a total of ~200,000 full-length transcripts, ~40% of which have novel exon junction chains. To capture and compute on the three sources of transcript structure diversity, we introduce a gene and transcript annotation framework that uses triplets representing the transcript start site, exon junction chain, and transcript end site of each transcript. Using triplets in a simplex representation demonstrates how promoter selection, splice pattern, and 3′ processing are deployed across human tissues, with nearly half of multitranscript protein coding genes showing a clear bias toward one of the three diversity mechanisms. Evaluated across samples, the predominantly expressed transcript changes for 74% of protein coding genes. In evolution, the human and mouse transcriptomes are globally similar in types of transcript structure diversity, yet among individual orthologous gene pairs, more than half (57.8%) show substantial differences in mechanism of diversification in matching tissues. This initial large-scale survey of human and mouse long-read transcriptomes provides a foundation for further analyses of alternative transcript usage, and is complemented by short-read and microRNA data on the same samples and by epigenome data elsewhere in the ENCODE4 collection.

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Section: Sample-specific and Global Changes In Predominantmentioning

confidence: 99%

The ENCODE4 long-read RNA-seq collection reveals distinct classes of transcript structure diversity

Reese

Williams

Balderrama-Gutierrez

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Herein, the ADAMTS family is involved in multiple processes in organism development and disease, including fibrosis, 11 , 12 , 13 and the COL family encodes collagen, which is a major component of the extracellular matrix, and Eln, which encodes elastic fibers. 14 Hence, we selected Thbs1 and P4ha3 for further validation.…”

Section: Discussionmentioning

confidence: 99%

Thrombospondin-1 and prolyl 4-hydroxylase subunit alpha 3 as potential biomarkers of salivary gland fibrosis

Zhang¹,

Li²,

Wang³

et al. 2023

Journal of Dental Sciences

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“…These cases are consistent with previous studies ( Metcalfe et al, 2000 ; Jakob et al, 2011 ; Jelsig et al, 2017 ) in which SVAS families had highly variable cardiovascular phenotypes ranging from asymptomatic to multiarterial severe stenosis. Such differences may be related to epigenetics ( Parrish et al, 2020 ; Procknow and Kozel, 2022 ), or some individuals may initially have undetected arterial stenosis then undergo self-healing, suggesting that pulmonary artery stenosis caused by elastin depletion has a high probability of undergoing gradual improvement as reported by Collins et al (2010) . Taken together, findings to date indicate that cardiac screening and genetic counseling should be administered to relatives of SVAS patients, as unaffected carriers may give birth to severely affected individuals.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of novel elastin gene mutations in eleven families with supravalvular aortic stenosis

Zhou

Wu²,

Xu³

et al. 2022

Front. Genet.

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Background: Supravalvular aortic stenosis (SVAS) is a rare congenital heart disease affecting approximately 1 in 25,000 live births. In some patients it is accompanied by pulmonary artery stenosis, particularly of pulmonary artery branches. Chronic stenosis can lead to cardiac hypertrophy and even circulatory failure. Familial autosomal dominant SVAS is frequently associated with elastin (ELN) gene mutations, whereas Williams-Beuren syndrome is a complex developmental disorder caused by heterozygous microdeletions of 26–28 genes at 7q11.23, including ELN.Methods: Whole-exome sequencing was performed in 42 individuals from 11 Chinese families with SVAS to identify the pathogenic gene mutations involved. Aortic tissue was obtained for histological analyses, and quantitative reverse-transcription-PCR and western blotting were used to verify the expression of elastin molecules.Results: Five point mutations and six frameshift mutations in the ELN gene were detected in the peripheral blood of all investigated families. Nine were nonsense mutations that result in premature stop codons, and the other two were missense mutations. All variants were heterozygous. Nine of the variants were novel, and have not been included in databases or previously reported. One mutation occurred in individuals from two different families. Reduced elastin protein expression was evident in patients’ aortic tissue.Conclusions: The novel mutations of ELN were found to be pathogenic, which confirmed by reduced elastin expression and leads to SVAS. Thus, detailed cardiac testing and genetic counseling are warranted for patients and asymptomatic individuals with these mutations.

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Emerging mechanisms of elastin transcriptional regulation

Cited by 6 publications

References 144 publications

The ENCODE4 long-read RNA-seq collection reveals distinct classes of transcript structure diversity

The ENCODE4 long-read RNA-seq collection reveals distinct classes of transcript structure diversity

Thrombospondin-1 and prolyl 4-hydroxylase subunit alpha 3 as potential biomarkers of salivary gland fibrosis

Identification and characterization of novel elastin gene mutations in eleven families with supravalvular aortic stenosis

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