An alternative retinoic acid-responsive Stra6 promoter regulated in response to retinol deficiency
Authors: Joseph Scandura
Vasundhra Kashyap
Kristian B Laursen
Lorraine J Gudas
Journal: Journal of Biological Chemistry (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: CRISPR/Cas; Cell Differentiation; Embryonic Stem Cell; Epigenetics; Retinoic Acid
Affiliations: From the Pharmacology Department and., the Department of Medicine, Weill Cornell Medical College of Cornell University, New York, New York 10065., From the Pharmacology Department and the Department of Medicine, Weill Cornell Medical College of Cornell University, New York, New York 10065 .

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 ‚à?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 RARŒ≥ and RXRŒ± 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 RARŒ≥. 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 RARŒ≥(-/-) 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. 

Retracted: No

PubPeer comments:
  Fig. 4 miR-376a regulates OS cell behaviors via targeting FBXO11. ... **c cell invasion**... in OS cells transfected with pcFBXO11, pcDNA3.1, si-FBXO11, NC-siR, or pcFBXO11 and miR-376a mimic . Overlaps between purportedly different conditions.  More importantly, at least one of the panels is a photomosaic, with multiple copies of the same cell.  , 
 This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels. Despite these similarities, these papers are authored by researchers from different departments and institutes, with almost no overlap in authors. The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing A more detailed description of this set of papers, suspected to all be generated by a common source, a paper mill , can be found here: * https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers (January 2020) * https: scienceintegritydigest.com 2020 02 21 the-tadpole-paper-mill (February 2020) The same paper mill has been described in these papers: * Jana Christopher - Systematic fabrication of scientific images revealed - FEBS Letters (2018) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13201 * Jennifer A Byrne and Jana Christopher - Digital magic, or the dark arts of the 21st centuryu2014how can journals and peer reviewers detect manuscripts and publications from paper mills? - FEBS Letters (2020) - https: febs.onlinelibrary.wiley.com doi full 10.1002 1873-3468.13747 , 
 2020 retraction. https: link.springer.com article 10.1007 s13577-020-00386-y This article [1] has been retracted by the editors because the data are unreliable. It appears that the images in Fig. 4c have been re-used but labelled as different conditions, specifically: Part of the panel labelled as J2OS cell line transfected with pcDNA3.1 appears to have been reproduced in the panel labelled as MG63 cells transfected with the same plasmid. Part of the panel labelled as J2OS cell line transfected with miR-376a mimic appears to have been re-used in two other panels for si-FBXO11 in both cell lines. There appear to be multiple copies of a distinctly shaped cell in the NC-siR panel for MG63 cell line. The authors were asked to provide raw data for this figure, but were unable to do so. Author Jianyang Chen stated on behalf of all co-authors that they agree to this retraction. Reference 1. Xu, Q., Cheng, L., Chen, J. et al. miR-376a inhibits the proliferation and invasion of osteosarcoma by targeting FBXO11. Human Cell 32, 390u2013396 (2019). https: doi.org 10.1007 s13577-019-00256-2 ,