Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism

Corso-Díaz, Ximena; Gentry, James; Rebernick, Ryan; Jaeger, Catherine; Brooks, Matthew; Asten, Freekje van; Kooragayala, Keshav; Gieser, Linn; Nellissery, Jacob; Covián, Raúl; Cogliati, Tiziana; Mondal, Anupam; Jiang, Ke; Swaroop, Anand

doi:10.1016/j.celrep.2020.107525

Cited by 27 publications

(20 citation statements)

References 91 publications

(125 reference statements)

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“…Beyond that, PRPH2, CDHR1, ABCA4, and GUCA1A were downregulated in a mouse knockout model of NEUROD1 (Neuronal Differentiation 1) gene ( Ochocinska et al, 2012 ). Perturbations in the transcription factors ONECUT2 (One Cut Homeobox 2) , EGR1 (Early Growth Response 1) , NRL (Neural Retina Leucine Zipper), and VAX2 (Ventral Anterior Homeobox 2) seems to affect the expression of the genes found in association with CACD in this review, all based in knockout assays in mouse ( Alfano et al, 2011 ; Goetz et al, 2014 ; Oh et al, 2017 ; Han et al, 2018 ; Corso-Díaz et al, 2020 ). MECP2 (Methyl-CpG-Binding Protein 2) was also included in this group but is the unique factor not associated with retinal diseases or eye development, playing a substantial role in early neurodevelopment ( Urdinguio et al, 2008 ).…”

Section: Resultsmentioning

confidence: 90%

“…TTLL5 is expressed primarily in the testis and in the inner part of photoreceptors of the retina, in the base of the photoreceptor’s primary cilium ( Bedoni et al, 2016a ). Few recent associations with cone-rod dystrophies, including one that reports a TTLL5 multi-exon ( Reig et al, 1995a ; Hoyng et al, 1996b ; Kohl et al, 1997b ; Payne et al, 1998 ; Urdinguio et al, 2008 ; Alfano et al, 2011 ; Ochocinska et al, 2012 ; Goetz et al, 2014 ; Oh et al, 2017 ; Han et al, 2018 ; Corso-Díaz et al, 2020 ) deletion that causes cone-rod dystrophy, were found in a retrospective study with Arab families ( Westermann and Weber, 2003 ; Sergouniotis et al, 2014 ; Bedoni et al, 2016b ; Sun et al, 2016 ; Dias et al, 2017 ; Méjécase et al, 2020 ). Photoreceptors of mice with truncated alleles of TLL5 or of the Retinitis pigmentosa GTPase regulator ( RPGR ) gene exhibit no tubulin glutamylation (addition of glutamate molecules).…”

Section: Discussionmentioning

confidence: 99%

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New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy—Beyond Classical Gene Candidates

Camargo

Prezia²,

Shiokawa

et al. 2022

Front. Genet.

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Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that mainly affects the macula, resulting in progressive and usually profound visual loss. Being part of congenital retinal dystrophies, it may have an autosomal dominant or recessive inheritance and, until now, has no effective treatment. Given the shortage of genotypic information about the disease, this work systematically reviews the literature for CACD-causing genes. Three independent researchers selected 33 articles after carefully searching and filtering the Scielo, Pubmed, Lilacs, Web of Science, Scopus, and Embase databases. Mutations of six genes (PRPH2, GUCA1A, GUCY2D, CDHR1, ABCA4, and TTLL5) are implicated in the monogenic dominant inheritance of CACD. They are functionally related to photoreceptors (either in the phototransduction process, as in the case of GUCY2D, or the recovery of retinal photodegradation in photoreceptors for GUCA1A, or the formation and maintenance of specific structures within photoreceptors for PRPH2). The identified genetic variants do not explain all observed clinical features, calling for further whole-genome and functional studies for this disease. A network analysis with the CACD-related genes identified in the systematic review resulted in the identification of another 20 genes that may influence CACD onset and symptoms. Furthermore, an enrichment analysis allowed the identification of 13 transcription factors and 4 long noncoding RNAs interacting with the products of the previously mentioned genes. If mutated or dysregulated, they may be directly involved in CACD development and related disorders. More than half of the genes identified by bioinformatic tools do not appear in commercial gene panels, calling for more studies about their role in the maintenance of the retina and phototransduction process, as well as for a timely update of these gene panels.

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Section: Resultsmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy—Beyond Classical Gene Candidates

Camargo

Prezia²,

Shiokawa

et al. 2022

Front. Genet.

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show abstract

“…The msPIPE was applied to publicly-available human (accession number: PRJEB28044) [ 49 ] and mouse (accession number: PRJNA556668) WGBS datasets [ 50 ] (Additional file 2 : Table S1). The human dataset was generated from the pooled libraries of DNA obtained from the blood and sperm of six young men (18–24 years) and six old men (61–71 years), respectively.…”

Section: Resultsmentioning

confidence: 99%

msPIPE: a pipeline for the analysis and visualization of whole-genome bisulfite sequencing data

et al. 2022

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Background DNA methylation is an important epigenetic modification that is known to regulate gene expression. Whole-genome bisulfite sequencing (WGBS) is a powerful method for studying cytosine methylation in a whole genome. However, it is difficult to obtain methylation profiles using the WGBS raw reads and is necessary to be proficient in all types of bioinformatic tools for the study of DNA methylation. In addition, recent end-to-end pipelines for DNA methylation analyses are not sufficient for addressing those difficulties. Results Here we present msPIPE, a pipeline for DNA methylation analyses with WGBS data seamlessly connecting all the required tasks ranging from data pre-processing to multiple downstream DNA methylation analyses. The msPIPE can generate various methylation profiles to analyze methylation patterns in the given sample, including statistical summaries and methylation levels. Also, the methylation levels in the functional regions of a genome are computed with proper annotation. The results of methylation profiles, hypomethylation, and differential methylation analysis are plotted in publication-quality figures. The msPIPE can be easily and conveniently used with a Docker image, which includes all dependent packages and software related to DNA methylation analyses. Conclusion msPIPE is a new end-to-end pipeline designed for methylation calling, profiling, and various types of downstream DNA methylation analyses, leading to the creation of publication-quality figures. msPIPE allows researchers to process and analyze the WGBS data in an easy and convenient way. It is available at https://github.com/jkimlab/msPIPE and https://hub.docker.com/r/jkimlab/mspipe.

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“…These so called “hotspots” of differential DNA methylation could suggest loci in these regions are prone to epigenetic alterations including methylation. Transposable elements (TEs) tend to be heavily methylated and have been reported to have involvement in developmental processes in almond, such as the juvenile-to-adult transition (Han et al ., 2018; Corso-Díaz et al ., 2020; Wyler et al ., 2020), suggesting the “hotspots” identified in almond in this study could contain TE sequences. This type of pattern has been documented in other species such as rice, were a study on salt tolerance identified DMRs that tended to cluster on specific chromosomes and were typically associated with TEs on these chromosomes (Ferreira et al ., 2019).…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation and small RNA expression are associated with increased age in almond (Prunus dulcis[Mill.] D.A. Webb) accessions

et al. 2021

Preprint

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The focus of this study is to profile changes in DNA methylation occurring with increased age in almond breeding germplasm in an effort to identify possible biomarkers of age that can be used to assess the potential individuals have to develop aging-related disorders in this productive species. To profile DNA methylation in almond germplasm, 70 methylomes were generated from almond individuals representing three age cohorts (11, 7, and 2-years old) using an enzymatic methyl-seq approach followed by analysis to call differentially methylated regions (DMRs) within these cohorts. Weighted chromosome-level methylation analysis reveals hypermethylation in 11-year-old almond breeding selections when compared to 2-year-old selections in the CG and CHH contexts. A total of 17 consensus DMRs were identified in all age-contrasts, and one of these DMRs contains the sequence for miR156, a microRNA with known involvement in regulating the juvenile-to-adult transition. Almond shows a pattern of hypermethylation with increased age, and this increase in methylation may be involved in regulating the vegetative transition in almond. The identified DMRs could function as putative biomarkers of age in almond following validation in additional age groups.

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Genome-wide Profiling Identifies DNA Methylation Signatures of Aging in Rod Photoreceptors Associated with Alterations in Energy Metabolism

Cited by 27 publications

References 91 publications

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy—Beyond Classical Gene Candidates

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy—Beyond Classical Gene Candidates

msPIPE: a pipeline for the analysis and visualization of whole-genome bisulfite sequencing data

Hypermethylation and small RNA expression are associated with increased age in almond (Prunus dulcis[Mill.] D.A. Webb) accessions

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