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Satyabrata Sinha, Marycharmain Belcastro, Dongquan Chen, Maxim Sokolov; Transcriptional Feedback of the Chaperonin CCT in Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):41.
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© ARVO (1962-2015); The Authors (2016-present)
Chaperonin Containing TCP-1 (CCT) is a large protein complex that mediates the folding of nascent polypeptides in eukaryotic cells. Using a mouse model having suppressed CCT activity in its photoreceptors, we previously identified several protein networks critically affected by this manipulation. Here we explored the transcriptional and posttranscriptional levels of response in this model.
Global expression profiles were determined using GeneChip Exon arrays. Data were refined through T statistics after filtering for minimum intensity, background, fold changes and RMA-normalization. FDR was applied and the affected pathways were identified by Ingenuity Pathway Analysis. Selected targets were further validated by quantitative RT-PCR, Western blotting and immunofluorescence microscopy.
We identified 27 down-regulated and 4 up-regulated genes responsive to the CCT suppression. The visual signaling pathway represented the largest down-regulated network, with three distinct types of responses. The first type was uniquely represented by the Gnat1 gene, whose transcript was down-regulated by 24 fold, and the protein product was undetectable. The second type included Rho, PDE6a and PDE6b genes which were characterized by significant 3-4 fold reductions of both mRNA and protein levels. The third type was represented by Gng1, Prph2, Rom1, Rgs9, and Gnb5 genes down-regulated by 4-10 fold on the protein level only.
Our analysis revealed some previously unknown transcriptional feedback from the chaperonin CCT to several essential phototransduction genes. The possible mechanism of this feedback will be discussed.
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