WDR77 (WD repeat domain 77) is expressed during earlier lung development when cells are rapidly proliferating, but is absent from adult lung. It is re-activated during lung tumorigenesis and is essential for lung cancer cell proliferation. Signalling pathways/molecules that control WDR77 gene expression are unknown. Promoter mapping, gel shift assay and ChIP revealed that the WDR77 promoter contains bona fide response elements for E2F and GATA transcriptional factors as demonstrated in prostate cancer, lung cancer and erythroid cells, as well as in mouse lung tissues. The WDR77 promoter is transactivated by E2F1, E2F3, GATA1 and GATA6, but suppressed by E2F6, GATA1 and GATA3 in prostate cancer PC3 cells. WDR77 expression is associated with E2F1, E2F3, GATA2 and GATA6 occupancy on the WDR77 gene, whereas, in contrast, E2F6, GATA1 and GATA3 occupancy is associated with the loss of WDR77 expression during erythroid maturation and lung development. More importantly, the loss of WDR77 expression that results from E2F and GATA switches is required for cellular differentiation of erythroid and lung epithelial cells. In contrast, lung cancer cells avoid post-mitotic differentiation by sustaining WDR77 expression. Altogether, the present study provides a novel molecular mechanism by which WDR77 is regulated during erythroid and lung development and lung tumorigenesis.
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August 2016
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A schematic representation for the process of mitophagy in skeletal muscle. For a detailed coverage of the regulation of mitochondrial function in muscle, see the review by Hood et al. (Volume 473, Issue 15, pages 2295–2314). - PDF Icon PDF LinkFront Matter
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Research Article|
July 28 2016
E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells
Min Yu;
Min Yu
*School of Life Sciences, Yunnan University, Yunnan, China
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Ulrica Wang;
Ulrica Wang
†Atowah High School, Woodstock, GA 30189, U.S.A.
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Zhengxin Wang
Zhengxin Wang
1
‡Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, U.S.A.
1To whom correspondence should be addressed (email zwang@cau.edu).
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Publisher: Portland Press Ltd
Received:
February 18 2016
Revision Received:
May 26 2016
Accepted:
June 06 2016
Accepted Manuscript online:
June 07 2016
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem J (2016) 473 (15): 2331–2343.
Article history
Received:
February 18 2016
Revision Received:
May 26 2016
Accepted:
June 06 2016
Accepted Manuscript online:
June 07 2016
Citation
Min Yu, Ulrica Wang, Zhengxin Wang; E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells. Biochem J 1 August 2016; 473 (15): 2331–2343. doi: https://doi.org/10.1042/BCJ20160130
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