Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development
Authors: Gang Wei
Iouri Chepelev
Keji Zhao
Helen Y Wang
Qingtian Li
Qingyuan Zhu
Rong-Fu Wang
Journal: PLoS Genetics (2014)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Histone demethylases; Jumonji domain containing-3 (Jmjd3); gene expression regulation; embryonic development; knockout mice
Affiliations: Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, Texas, United States of America., Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America., CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China., Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, United States of America.

Abstract:  Histone demethylases have emerged as important players in developmental processes. Jumonji domain containing-3 (Jmjd3) has been identified as a key histone demethylase that plays a critical role in the regulation of gene expression; however, the in vivo function of Jmjd3 in embryonic development remains largely unknown. To this end, we generated Jmjd3 global and conditional knockout mice. Global deletion of Jmjd3 induces perinatal lethality associated with defective lung development. Tissue and stage-specific deletion revealed that Jmjd3 is dispensable in the later stage of embryonic lung development. Jmjd3 ablation downregulates the expression of genes critical for lung development and function, including AQP-5 and SP-B. Jmjd3-mediated alterations in gene expression are associated with locus-specific changes in the methylation status of H3K27 and H3K4. Furthermore, Jmjd3 is recruited to the SP-B promoter through interactions with the transcription factor Nkx2.1 and the epigenetic protein Brg1. Taken together, these findings demonstrate that Jmjd3 plays a stage-dependent and locus-specific role in the mouse lung development. Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development. 

Retracted: No

PubPeer comments:
 Figure 3. * Blue boxes: Panels a (Day 14) and b (Day 28) appear to show the same tissue section, albeit at a different zoom factor. ![file] , 
 Erratum, August 2022: https: onlinelibrary.wiley.com doi 10.1002 bit.27917  This erratum is being published to correct the mistake in Figure 3 caption, we wrote Figures 3a and 3b for different magnifications for H E staining images. The Figure 3 caption u201cFigure 3. Histological and immunohistochemical staining of the cell-seeded hydrogels. (a and b) Sections were stained with H E at (a) day 14 and (b) day 28; (c and d) sections were stained with Safranin O for GAGs after (c) 14 days and (d) 28 days of incubation; and (f and g) sections were immunohistochemically stained for collagen type II after (e) 14 days and (f) 28 days of incubation. (scale bar [a] 200u2009mm, 4; [bu2013g] 50u2009mm, 10.)u201d should read u201cFigure 3. Histological and immunohistochemical staining of the cell-seeded hydrogels. (a and b) Sections were stained with H E at (a) day 14 at a low magnification and (b) at a high magnification; (c and d) sections were stained with Safranin O for GAGs after (c) 14 days and (d) 28 days of incubation; and (f and g) sections were immunohistochemically stained for collagen type II after (e) 14 days and (f) 28 days of incubation (scale bar [a] 200u2009mm, 4; [bu2013g] 50u2009mm, 10.).u201d All other parts are unchanged. The authors regret these errors. ,