Regulation of the p19Arf/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence‐prone SAMP8 mice

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1‐NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age‐related changes in B1‐NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence‐accelerated‐prone mice (SAMP8) relative to senescence‐accelerated‐resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the study of aging. We have found that the B1‐NSC compartment is transiently expanded in young SAMP8 relative to SAMR1 mice, resulting in disturbed cytoarchitecture of the SEZ, B1‐NSC hyperproliferation, and higher yields of primary neurospheres. These unusual features are, however, accompanied by premature loss of B1‐NSCs. Moreover, SAMP8 neurospheres lack self‐renewal and enter p53‐dependent senescence after only two passages. Interestingly, in vitro senescence of SAMP8 cells could be prevented by inhibition of histone acetyltransferases and mimicked in SAMR1 cells by inhibition of histone deacetylases (HDAC). Our data indicate that expression of the tumor suppressor p19, but not of p16, is increased in SAMP8 neurospheres, as well as in SAMR1 neurospheres upon HDAC inhibition, and suggest that the SAMP8 phenotype may, at least in part, be due to changes in chromatin status. Interestingly, acute HDAC inhibition in vivo resulted in changes in the SEZ of SAMR1 mice that resembled those found in young SAMP8 mice.     

组蛋白乙酰转移酶的研究进展

组蛋白乙酰化与基因转录等生物效应有密切的关系,组蛋白乙酰化主要是由组蛋白乙酰转移酶催化的。 要介绍了基因转录有关组蛋白乙酰转移酶,包括ＨＡＴＡ／Ｇｃｎ５ｐ、ｐ３００／ＣＢＰ、ｐ／ＣＡＦ、ＡＣＴＲ、Ｓｒｃ１、ＴＡＦ Ⅱ ２５０、Ｅｌｐ３等的来源,与其相互作用的蛋白质及其主要功能。     

染色质修饰酶在记忆中的作用

学习记忆的形成依赖于转录机制.近年研究发现,染色质修饰在基因表达调节中起重要作用.组蛋白乙酰化和去乙酰化是染色质修饰中最为常见调节方式,参与基因的转录调控.乙酰化可以激活转录,促进记忆的形成.组蛋白去乙酰化酶抑制剂可以增强突触可塑性,改善记忆损伤.因此,对于染色质修饰的深入研究,不仅有助于阐明记忆形成的分子机制,而且对记忆相关疾病的治疗以及新药物研发也具有重要指导意义.本文主要就组蛋白乙酰转移酶调节基因转录以及组蛋白去乙酰化酶抑制剂促进记忆形成的作用机理进行综述.     

转录因子在植物干旱应激中的功能研究进展

转录因子是一种多功能蛋白,在感知应激信号、应答相应应激基因表达及传导应激信号中起着关键作用。干旱是影响植物生长发育的主要非生物胁迫之一。为了适应干旱环境,植物发展了复杂的分子机制,其中转录因子可同时控制多种途径调控干旱应激,是操纵调控和应激响应途径的有力工具。近年来,越来越多的植物转录因子的功能被阐明,了解转录因子在干旱应激的功能,对植物的工程抗旱有重要的实践意义。综述转录因子在植物干旱应激中的功能研究进展,以期为今后转录因子的研究和利用提供理论依据,培育具有较强抗旱能力的植物。     

脂肪细胞分化相关转录因子的结构和功能

关于脂肪细胞分化调控的研究主要集中在转录因子的作用上。目前了解得比较清楚的分化转录因子有多种,其中CAAT增强子结合蛋白家族（C/EBPs）中的C／EBPα和过氧化物酶体增殖物激活受体家族（PPARs）中的PPARy是转录调控中起主要作用的两种因子。两者有各自的结构特点和功能,但在脂肪细胞中它们之间相互协同促进细胞的分化成熟。本文主要就C／EBPs和PPARs家族中主要成员的结构和功能及相互作用进行综述。     

转录因子对B细胞发育的调控作用

Ｂ细胞同其他血细胞一样,也是由多能造血干细胞发育为祖细胞,再发育成 末成熟细胞的。发育过程中,向Ｂ细胞发育的前 细胞逐渐推动向其他谱系发育的潜能,Ｂ细胞谱系特征性基因开始表达。近来的研究表明,Ｂ细胞发育过程中有多种转录因子参与,它们调节多种重要基因的转录,保证Ｂ细胞的正常发育。本文综述了与Ｂ细胞发育相关转录因子的最新研究进展。     

WRKY转录因子功能的多样化

WRKY是植物中一类重要的转录因子家族,其共同的特点是含有高度保守的核心氨基酸序列WRKYGQK,在C-末端有一个锌指结构。WRKY受到病原菌、损伤、SA(salicylic acid)等因子的诱导后表达,特异性识别(T)(T)TGAC(C/T)序列(W-box),调节基因的表达而参与许多生理过程,如抗病、损伤、生长发育以及衰老等。该文主要介绍了WRKY的结构特点及其功能的研究进展。     

Targeting histone acetylation dynamics and oncogenic transcription by catalytic P300/CBP inhibition

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Control of ribosomal RNA synthesis by hematopoietic transcription factors

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