Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Conditional knockdown of DNA methyltransferase-1 (Dnmt1) reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

ABSTRACT: To explore the epigenetic contribution to retinal development, we generated conditional knockout alleles of DNA methytransferase-1 (Dnmt1) mediated by Rx-Cre in mice. The results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. Retinal samples were harvested from both Dnmt1 mutant and wt animals at embryonic day 16.5 and postnatal days 0.5, 6.5, and 10.5 for microarray analysis. Each experiment was performed with biological quadruplicates. One microgram of total RNA was used for cDNA systhesis in target molecule production.

ORGANISM(S): Mus musculus

SUBMITTER: Matthew Brooks

PROVIDER: E-GEOD-43951 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis.

Nasonkin Igor O IO Merbs Shannath L SL Lazo Kevin K Oliver Verity F VF Brooks Matthew M Patel Krushangi K Enke Raymond A RA Nellissery Jacob J Jamrich Milan M Le Yun Z YZ Bharti Kapil K Fariss Robert N RN Rachel Rivka A RA Zack Donald J DJ Rodriguez-Boulan Enrique J EJ Swaroop Anand A

Development (Cambridge, England) 20130213 6

Dysfunction or death of photoreceptors is the primary cause of vision loss in retinal and macular degenerative diseases. As photoreceptors have an intimate relationship with the retinal pigment epithelium (RPE) for exchange of macromolecules, removal of shed membrane discs and retinoid recycling, an improved understanding of the development of the photoreceptor-RPE complex will allow better design of gene- and cell-based therapies. To explore the epigenetic contribution to retinal development we ...[more]

PMID: 23406904

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Project description:<h4>Summary</h4>Primary cilia are key sensory organelles whose dysfunction leads to ciliopathy disorders such as Bardet-Biedl syndrome (BBS). Retinal degeneration is common in ciliopathies, since the outer segments (OSs) of photoreceptors are highly specialized primary cilia. BBS1, encoded by the most commonly mutated BBS-associated gene, is part of the BBSome protein complex. Using a new bbs1 zebrafish mutant, we show that retinal development and photoreceptor differentiation are unaffected by Bbs1-loss, supported by an initially unaffected transcriptome. Quantitative proteomics and lipidomics on isolated OSs show that Bbs1 is required for BBSome-entry into OSs and that Bbs1-loss leads to accumulation of membrane-associated proteins in OSs, with enrichment in proteins involved in lipid homeostasis. Disruption of the tightly regulated OS lipid composition with increased OS cholesterol content are paralleled by early functional visual deficits, which precede progressive OS morphological anomalies. Our findings identify a new role for Bbs1/BBSome in OS lipid homeostasis and suggest a new pathomechanism underlying retinal degeneration in BBS. Data availability:The proteomic data generated in this study have been deposited in PRIDE repository under accession code <a href='https://www.ebi.ac.uk/pride/archive/projects/PXD026646' rel='noopener noreferrer' target='_blank'>PXD026646</a> for the OS proteome and <a href='https://www.ebi.ac.uk/pride/archive/projects/PXD030522' rel='noopener noreferrer' target='_blank'>PXD030522</a> for the whole eye lysate proteome [<a href='https://www.ebi.ac.uk/pride' rel='noopener noreferrer' target='_blank'>https://www.ebi.ac.uk/pride</a>].The RNAseq data generated in this study have been deposited in the SRA repository under the BioProject accession number PRJNA789116 [<a href='https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA789116' rel='noopener noreferrer' target='_blank'>https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA789116</a>].

Dataset Information

Conditional knockdown of DNA methyltransferase-1 (Dnmt1) reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

Publications

Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis.

Similar Datasets

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