Upregulation of PHLDA2 in Dicer knockdown HEK293 cells
Upregulation of PHLDA2 in Dicer knockdown HEK293 cells
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Dicer 敲除 HEK293 细胞中 PHLDA2 的上调
DOI：
10.1016/j.bbagen.2007.01.004
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发表时间：
2007-05-01
影响因子：
3
通讯作者：
Ren, Hong
中科院分区：
文献类型：
--
作者：
Tang, Kai-Fu;Wang, Yan;Ren, Hong
据报道，脊椎动物中依赖rnai的染色质沉默并不局限于着丝粒。为了解决RNAi机制是否可以调节印迹基因的染色质结构，我们在HEK293细胞中敲除Dicer，发现11p15.5印迹基因域中的几个基因之一PHLDA2的表达特异性上调。这伴随着PHLDA2位点向更活化的染色质的转变，正如H3K9乙酰化的变化所表明的那样，然而，该位点的甲基化状态没有受到影响。此外，我们发现PHLDA2在血清剥夺或接触抑制诱导的生长受阻的HEK293细胞中下调。这表明PHLDA2上调可能是Dicer缺失的直接结果，而不是Dicer敲低引起的生长停滞的结果。考虑到有报道称PHLDA2敲除小鼠胎盘生长一致，以及PHLDA2在小鼠中过表达导致生长抑制，我们推测PHLDA2可能是Dicer敲除小鼠中Dicer缺陷细胞生长速率降低和早期胚胎致死的候选因素。(c) 2007 Elsevier B.V.版权所有
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. (c) 2007 Elsevier B.V. All rights reserved.