Upregulation of PHLDA2 in Dicer knockdown HEK293 cells |
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Authors: | Kai-Fu Tang Yan Wang Pengfei Wang Min Chen Yao Chen Huai-Dong Hu Peng Hu Bo Wang Wenjie Yang Hong Ren |
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Affiliation: | 1. Key Laboratory of Molecular Biology for Infectious Diseases of State Ministry of Education, The second Affiliated Hospital, Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, PR China;2. Department of Emergency, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China;3. Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China;4. The Institute of Psychology, Chinese Academy of Sciences (CAS), Beijing 100101, PR China;5. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA |
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Abstract: | It has been reported that RNAi-dependent chromatin silencing in vertebrates is not restricted to the centromeres. To address whether RNAi machinery could regulate the chromatin structure of imprinted genes, we knocked down Dicer in HEK293 cells and found that the expression of PHLDA2, one of the several genes in the imprinted gene domain of 11p15.5, was specifically upregulated. This was accompanied by a shift towards more activated chromatin at PHLDA2 locus as indicated by change in H3K9 acetylation, however, the methylation state at this locus was not affected. Furthermore, we found that PHLDA2 was downregulated in growth-arrested HEK293 cells induced by either serum deprivation or contact inhibition. This suggests that PHLDA2 upregulation might be a direct result of Dicer depletion rather than the consequence of growth arrest induced by Dicer knockdown. Considering the reports that there is consistent placental outgrowth in PHLDA2 knockout mice and that PHLDA2 overexpression in mice causes growth inhibition, we speculate that PHLDA2 may be a candidate for contributing to the reduced growth rate of Dicer-deficient cells and the very early embryonic lethality in Dicer knockout mice. |
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Keywords: | PHLDA2 Dicer Genomic imprinting Embryonic lethality Growth arrest |
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