浙江大学两研究组接连发文获研究新进展

【字体: 时间:2011年09月22日 来源:生物通

编辑推荐:

  浙江大学前身求是书院成立于1897年,为中国人自己最早创办的新式高等学府之一。目前的浙江大学由浙江大学、杭州大学、浙江农业大学、浙江医科大学合并组建而成。近期浙江大学两个研究组获得了两项研究新进展:跨膜蛋白在叶绿体发育等方面的新作用,以及主动去甲基化调控新机制。

  生物通报道:浙江大学前身求是书院成立于1897年,为中国人自己最早创办的新式高等学府之一。目前的浙江大学由浙江大学、杭州大学、浙江农业大学、浙江医科大学合并组建而成。近期浙江大学两个研究组获得了两项研究新进展:跨膜蛋白在叶绿体发育等方面的新作用,以及主动去甲基化调控新机制。

第一篇文章“A chloroplast envelope membrane protein containing a putative LrgB domain related to the control of bacterial death and lysis is required for chloroplast development in Arabidopsis thaliana”中,浙江大学遗传学研究所的研究人员利用反向遗传学方法,发现了拟南芥AtLrgB蛋白在叶绿体发育、碳同化物分配和叶片衰老中的作用。这对于深入了解跨膜蛋白对于植物发育,及衰老机制的作用具有重要意义。

细菌质膜上的CidAB/LrgAB体系和真核线粒体外膜上的Bax/Bcl-2体系,都是高度疏水的跨膜蛋白,调控着细胞的死亡。植物叶绿体外被膜(envelope membrane)存在着上CidAB/LrgAB的同源蛋白,但它们的功能没有报道。

遗传学研究所朱睦元教授实验室王君晖小组通过反向遗传学方法,发现拟南芥叶绿体中常见蛋白AtLrgB具有之前未知的调控叶绿体发育,碳同化物分配,以及叶片衰老的新作用。

第二篇文章中,研究人员揭示了成体干细胞终端分化中存在DNA主动去甲基化调控方式,而且生长阻滞与DNA损伤诱导蛋白Gadd45a在该过程中发挥了关键作用。这一研究成果公布在JBC杂志上。

DNA甲基化和去甲基化是表观遗传调控的两种重要方式。目前人们对DNA甲基化已开展了系统研究,但对DNA去甲基化尚缺乏深入认识。长期来认为DNA去甲基化是一个依赖DNA复制的被动去甲基的过程,对于机体内是否存在主动去甲基化调控机制是长期以来备受关注的热点科学问题。

在这篇文章中,研究人员以间充质干细胞成骨分化为实验模型,揭示了成体干细胞终端分化中存在DNA主动去甲基化调控方式,而且生长阻滞与DNA损伤诱导蛋白Gadd45a在该过程中发挥了关键作用。研究发现,Gadd45a介导的成骨基因表达的去甲基化调控主要发生于启动子的CpG岛外(island shore)中等密度区,而非通常认为的高密度CpG岛,而且Gadd45a介导的主动去甲基化主要发生在若干特定的CpG位点上,如Dlx5的-913和-800、Runx2的-820和-808、BGP的-1003以及Osterix的-727和-632 CpG位点,提出在DNA主动去甲基化过程中可能存在一种位点特异性去甲基化机制。研究还发现,Gadd45a通过与启动子直接结合而发挥作用,它对成骨分化基因的主动去甲基化调控可能是通过NER途径实现的。

原文摘要:

A chloroplast envelope membrane protein containing a putative LrgB domain related to the control of bacterial death and lysis is required for chloroplast development in Arabidopsis thaliana

Summary
A protein encoded by At1g32080 was consistently identified in proteomic studies of Arabidopsis chloroplast envelope membranes, but its function remained unclear. The protein, designated AtLrgB, may have evolved from a gene fusion of lrgA and lrgB. In bacteria, two homologous operons, lrgAB and cidAB, participate in an emerging mechanism to control cell death and lysis.•We aim to characterize AtLrgB using reverse genetics and cell biological and biochemical analysis.•AtLrgB is expressed in leaves, but not in roots. T-DNA insertion mutation of AtLrgB produced plants with interveinal chlorotic and premature necrotic leaves. Overexpression of full-length AtLrgB (or its LrgA and LrgB domains, separately), under the control of CaMV 35S promoter, produced plants exhibiting veinal chlorosis and delayed greening. At the end of light period, the T-DNA mutant had high starch and low sucrose contents in leaves, while the 35S:AtLrgB plants had low starch and high sucrose contents. Metabolite profiling revealed that AtLrgB appeared not to directly transport triose phosphate or hexose phosphates. In yeast cells, AtLrgB could augment nystatin-induced membrane permeability.•Our work indicates that AtLrgB is a new player in chloroplast development, carbon partitioning and leaf senescence, although its molecular mechanism remains to be established.

Gadd45a plays an essential role in active DNA demethylation during terminal osteogenic differentiation of adipose-derived mesenchymal stem cells

Methylation and demethylation of DNA are the complementary processes of epigenetic regulation. These two types of regulation influence a diverse array of cellular activities, including the maintenance of pluripotency and self-renewal in embryonic stem cells. It was generally believed that DNA demethylation occurs passively over several cycles of DNA replication, and that active DNA demethylation is rare. Recently, evidence for active DNA demethylation has been obtain in several cancer, neuronal, and embryonic stem cell lines. Studies in embryonic stem cell models, however, suggested that active DNA demethylation might be restricted to the early development of progenitor cells. Whether active demethylation is involved in terminal differentiation of adult stem cells is poorly understood. We provide evidence that active DNA demethylation does occur during terminal specification of stem cells in an adipose-derived mesenchymal stem cell (ADSC)-derived osteogenic differentiation model. The medium CpG regions in promoters of the Dlx5, Runx2, BGP and Osterix osteogenic lineage-specific genes were demethylated during the increase in gene expression associated with osteogenic differentiation. The growth arrest and DNA-damage-inducible protein Gadd45a was up-regulated in these processes. Knockdown of Gadd45a led to hypermethylation of Dlx5, Runx2, BGP, and Osterix promoters, followed by suppression of these genes expression and interruption of osteogenic differentiation. These results reveal that Gadd45a plays an essential role in gene-specific active DNA demethylation during adult stem cell differentiation. They enhance current knowledge of osteogenic specification and may also lead to a better understanding of the common mechanisms underlying epigenetic regulation in adult stem cell differentiation.


 

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