Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016599510> ?p ?o ?g. }
- W2016599510 endingPage "4366" @default.
- W2016599510 startingPage "4356" @default.
- W2016599510 abstract "Cellular uptake of vitamin A (retinol) is essential for many biological functions. The Stra6 protein binds the serum retinol-binding protein, RBP4, and acts in conjunction with the enzyme lecithin:retinol acyltransferase to facilitate retinol uptake in some cell types. We show that in embryonic stem (ES) cells and in some tissues, the Stra6 gene encodes two distinct mRNAs transcribed from two different promoters. Whereas both are all-trans-retinoic acid (RA)-responsive in ES cells, the downstream promoter contains a half-site RA response element (RARE) and drives an ∼13-fold, RA-associated increase in luciferase reporter activity. We employed CRISPR-Cas9 genome editing to show that the endogenous RARE is required for RA-induced transcription of both Stra6 isoforms. We further demonstrate that in ES cells, 1) both RARγ and RXRα are present at the Stra6 RARE; 2) RA increases co-activator p300 (KAT3B) binding and histone H3 Lys-27 acetylation at both promoters; 3) RA decreases Suz12 levels and histone H3 Lys-27 trimethylation epigenetic marks at both promoters; and 4) these epigenetic changes are diminished in the absence of RARγ. In the brains of WT mice, both the longer and the shorter Stra6 transcript (Stra6L and Stra6S, respectively) are highly expressed, whereas these transcripts are found only at low levels in RARγ−/− mice. In the brains of vitamin A-deficient mice, both Stra6L and Stra6S levels are decreased. In contrast, in the vitamin A-deficient kidneys, the Stra6L levels are greatly increased, whereas Stra6S levels are decreased. Our data show that kidneys respond to retinol deficiency by differential Stra6 promoter usage, which may play a role in the retention of retinol when vitamin A is low. Cellular uptake of vitamin A (retinol) is essential for many biological functions. The Stra6 protein binds the serum retinol-binding protein, RBP4, and acts in conjunction with the enzyme lecithin:retinol acyltransferase to facilitate retinol uptake in some cell types. We show that in embryonic stem (ES) cells and in some tissues, the Stra6 gene encodes two distinct mRNAs transcribed from two different promoters. Whereas both are all-trans-retinoic acid (RA)-responsive in ES cells, the downstream promoter contains a half-site RA response element (RARE) and drives an ∼13-fold, RA-associated increase in luciferase reporter activity. We employed CRISPR-Cas9 genome editing to show that the endogenous RARE is required for RA-induced transcription of both Stra6 isoforms. We further demonstrate that in ES cells, 1) both RARγ and RXRα are present at the Stra6 RARE; 2) RA increases co-activator p300 (KAT3B) binding and histone H3 Lys-27 acetylation at both promoters; 3) RA decreases Suz12 levels and histone H3 Lys-27 trimethylation epigenetic marks at both promoters; and 4) these epigenetic changes are diminished in the absence of RARγ. In the brains of WT mice, both the longer and the shorter Stra6 transcript (Stra6L and Stra6S, respectively) are highly expressed, whereas these transcripts are found only at low levels in RARγ−/− mice. In the brains of vitamin A-deficient mice, both Stra6L and Stra6S levels are decreased. In contrast, in the vitamin A-deficient kidneys, the Stra6L levels are greatly increased, whereas Stra6S levels are decreased. Our data show that kidneys respond to retinol deficiency by differential Stra6 promoter usage, which may play a role in the retention of retinol when vitamin A is low. Correction: An alternative retinoic acid-responsive Stra6 promoter regulated in response to retinol deficiency.Journal of Biological ChemistryVol. 295Issue 3PreviewVOLUME 290 (2015) PAGES 4356–4366 Full-Text PDF Open Access" @default.
- W2016599510 created "2016-06-24" @default.
- W2016599510 creator A5025300408 @default.
- W2016599510 creator A5055444971 @default.
- W2016599510 creator A5056452569 @default.
- W2016599510 creator A5089514537 @default.
- W2016599510 date "2015-02-01" @default.
- W2016599510 modified "2023-10-11" @default.
- W2016599510 title "An Alternative Retinoic Acid-responsive Stra6 Promoter Regulated in Response to Retinol Deficiency" @default.
- W2016599510 cites W1550965756 @default.
- W2016599510 cites W1933874 @default.
- W2016599510 cites W1967586552 @default.
- W2016599510 cites W1977345799 @default.
- W2016599510 cites W1986228299 @default.
- W2016599510 cites W1987604582 @default.
- W2016599510 cites W1993296289 @default.
- W2016599510 cites W1993569116 @default.
- W2016599510 cites W1994936206 @default.
- W2016599510 cites W1996813404 @default.
- W2016599510 cites W1997653785 @default.
- W2016599510 cites W1999132350 @default.
- W2016599510 cites W2004211176 @default.
- W2016599510 cites W2011792658 @default.
- W2016599510 cites W2012793421 @default.
- W2016599510 cites W2013840838 @default.
- W2016599510 cites W2014407862 @default.
- W2016599510 cites W2015416439 @default.
- W2016599510 cites W2017055517 @default.
- W2016599510 cites W2017461303 @default.
- W2016599510 cites W2021402522 @default.
- W2016599510 cites W2038141086 @default.
- W2016599510 cites W2045894871 @default.
- W2016599510 cites W2054672812 @default.
- W2016599510 cites W2057249117 @default.
- W2016599510 cites W2060140841 @default.
- W2016599510 cites W2064815984 @default.
- W2016599510 cites W2070421130 @default.
- W2016599510 cites W2070696096 @default.
- W2016599510 cites W2079457812 @default.
- W2016599510 cites W2085312769 @default.
- W2016599510 cites W2087764271 @default.
- W2016599510 cites W2098281422 @default.
- W2016599510 cites W2099671436 @default.
- W2016599510 cites W2104030002 @default.
- W2016599510 cites W2104748610 @default.
- W2016599510 cites W2108691372 @default.
- W2016599510 cites W2111709760 @default.
- W2016599510 cites W2128746061 @default.
- W2016599510 cites W2129235226 @default.
- W2016599510 cites W2131366061 @default.
- W2016599510 cites W2131525001 @default.
- W2016599510 cites W2139670264 @default.
- W2016599510 cites W2140199830 @default.
- W2016599510 cites W2141947536 @default.
- W2016599510 cites W2145555735 @default.
- W2016599510 cites W2150937837 @default.
- W2016599510 cites W2155063875 @default.
- W2016599510 cites W2168887077 @default.
- W2016599510 doi "https://doi.org/10.1074/jbc.m114.613968" @default.
- W2016599510 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4326842" @default.
- W2016599510 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25544292" @default.
- W2016599510 hasPublicationYear "2015" @default.
- W2016599510 type Work @default.
- W2016599510 sameAs 2016599510 @default.
- W2016599510 citedByCount "22" @default.
- W2016599510 countsByYear W20165995102015 @default.
- W2016599510 countsByYear W20165995102016 @default.
- W2016599510 countsByYear W20165995102017 @default.
- W2016599510 countsByYear W20165995102018 @default.
- W2016599510 countsByYear W20165995102019 @default.
- W2016599510 countsByYear W20165995102020 @default.
- W2016599510 countsByYear W20165995102021 @default.
- W2016599510 countsByYear W20165995102022 @default.
- W2016599510 countsByYear W20165995102023 @default.
- W2016599510 crossrefType "journal-article" @default.
- W2016599510 hasAuthorship W2016599510A5025300408 @default.
- W2016599510 hasAuthorship W2016599510A5055444971 @default.
- W2016599510 hasAuthorship W2016599510A5056452569 @default.
- W2016599510 hasAuthorship W2016599510A5089514537 @default.
- W2016599510 hasBestOaLocation W20165995101 @default.
- W2016599510 hasConcept C101762097 @default.
- W2016599510 hasConcept C104317684 @default.
- W2016599510 hasConcept C120197328 @default.
- W2016599510 hasConcept C132376346 @default.
- W2016599510 hasConcept C150194340 @default.
- W2016599510 hasConcept C153911025 @default.
- W2016599510 hasConcept C185592680 @default.
- W2016599510 hasConcept C2776745794 @default.
- W2016599510 hasConcept C2776940978 @default.
- W2016599510 hasConcept C2779573558 @default.
- W2016599510 hasConcept C2779963572 @default.
- W2016599510 hasConcept C2780914512 @default.
- W2016599510 hasConcept C2781121885 @default.
- W2016599510 hasConcept C41091548 @default.
- W2016599510 hasConcept C55493867 @default.
- W2016599510 hasConcept C64927066 @default.
- W2016599510 hasConcept C86803240 @default.
- W2016599510 hasConceptScore W2016599510C101762097 @default.