YY1 mechanism article published YY1机制文章发表

Yin-Yang1 (YY1), also known as “negative-positive 1” in Chinese. The transcript factor gets its name from the dual role of gene activation and repression, such as the “Ying-yang Tai Ji” pattern in Chinese culture. The discovery drew great attention in the academic world. As a representative work of Prof. Shi yang from Harvard University, the study has been published in Cell in 1991.YY1 was originally identified as a transcriptional repressor due to its interaction with the Polycomb repressive complex 2, which further initiates the tri-methylation ofK27 of histone 3 (H3K27me3) to repress specific genes. The PcG-independent gene expression-promoting functions of YY1 are also reported [1]. Moreover, YY1 has been reported to regulate cell proliferation and differentiation, and its deficiency in mice caused peri-implantation lethality during embryonic development [2]. It also plays a crucial role in tumor development [3]. In the pluripotency regulatory network [4], YY1 is a key factor. All these studies suggest the regulatory potency of YY1. Recent reports have demonstrated that YY1 can also function as a chromatin structure factor which mediates 3D interactions between enhancers and promoters [5]. The discovery quickly drives YY1 a star factor.However, how does YY1 regulate gene expression in pluripotency stem cells? Stem Cell Reports published an article of Prof. Ding junjun, Researcher Wang jia etc,in March 14th studied by Prof. Ding junjun, Researcher Wang jia etc., YY1 Positively Regulates Transcription by Targeting Promoters and Super-Enhancers through the BAF Complex in Embryonic Stem Cells.Super-enhancers (SEs) are clusters of enhancers seriating along the chromatins, upon which the enrichment of transcript factors and co-factors can drive related gene expression. SEs have a significant cell specificity for there are hundreds of SEs in a cell regulating key genes expression and determining cell fate [6].As a chromatin remodeling complex, BAF plays a significant role in both maintenance and establishment of stem cell pluripotency [7,8]. In somatic cells, chromatin structureisrelativealways more compact, thus the tight steric hindrancewhichhinders the enrichment of transcript factors and the following gene transcription. It is necessary that tThe exposure of abundant enhancers and pluripotency genes from the impactcompactchromatinis necessarystructureto promote transcriptionin pluripotency stem cells, in order to promote transcription. Therefore, BAF complex is of vital importance in chromatin remodeling.In the recentcurrentresearch, the team revealed the role of YY1 and BAF complex in the OCT4-mediated pluripotency network in mouse embryonic stem cells (mESCs). The interaction between YY1 and BAF complex promotes mESC proliferation and pluripotency. Moreover, the interaction alternative the mechanism of pluripotency regulation of YY1 through the switch from Myc-dependent pathway to Core-dependent pathway (via regulation of pluripotency genes such as Oct4, Nanog, Sall4 etc.).TheYY1-OCT4-BAF complexenriches at both promoter and super-enhancer regions to stimulate transcription. Thus, this study elucidates the role of YY1 in regulating pluripotency through its interaction with OCT4 and the BAF complex and the role of BAF complex in integrating YY1 into the core pluripotency network.  BAF作为一种染色体重组复合物,在干细胞多能性的维持和建立过程中都发挥着重要作用【7,8】。染色体在体细胞中往往结构相对紧密,而紧凑的位阻不利于转录因子的富集和基因的转录。在多能干细胞中需要大量增强子和多能性基因从紧凑的染色体上暴露出来以促进转录,这一过程需要BAF复合物发挥染色体重组的作用【9】。 在最新的这项研究中,研究团队经过深入的研究发现,BAF与YY1和OCT4蛋白在胚胎干细胞中相互作用以促进大量多能性基因的表达。BAF与YY1的相互作用一方面进一步加强了YY1的转录促进作用,另一方面,BAF的加入改变了YY1对多能性的调控机制,使得原本在多能性调控中YY1依赖的Myc通路转为依赖于Core通路(通过调控多能性基因Oct4、Nanog、Sall4等)。YY1、BAF和OCT4的相互作用使得该蛋白复合物不仅大量富集于启动子区域,还富集于超级增强子区域(下图),这也从另一方面验证了YY1的染色体结构蛋白的功能,暗示了YY1在多能干细胞中促进增强子启动子染色体三维互作的形成。 阴阳蛋白(Yin-Yang 1,为什么叫“Yin-Yang1”呢?因为这个转录因子既有激活因子又可以作为阻遏因子,兼二者而为一,像极了中国文化中的“阴阳太极图”。这一发现引起了学术界的极大关注,这是哈佛大学施扬教授研究学术生涯中代表性的重要工作之一,1991年发表在Cell杂志)YY1即可通过招募Polycomb家族蛋白复合物促进H3K27的三甲基化修饰,对基因转录起抑制作用,又可通过非依赖于Polycomb的机制对基因表达起促进作用【1】。缺失YY1的小鼠在胚胎发育过程中的会发生着床期致死【2】,YY1还被发现在多种肿瘤中起到促进肿瘤发生发展的作用【3】,而且,YY1存在于多能性调控网络中【4】。上述发现都说明了YY1功能的强大。 近期的研究发现,除了上述功能之外,YY1还起到染色体结构蛋白的功能,并介导增强子与启动子三维互作的产生【5】。这一发现使得YY1迅速成为引人注目的明星因子。 然而,YY1在多能性干细胞中是如何调控基因表达的呢? 3月14日,Stem Cell Reports发表了中山大学中山医学院丁俊军教授、王佳研究员等人题为YY1 Positively RegulatesTranscription by Targeting Promoters and Super-Enhancers through the BAFComplex in Embryonic Stem Cells的论文,报道了YY1通过与染色体重组蛋白复合物BFA相互作用在胚胎干细胞中靶向启动子和超级增强子来促进基因表达和维持干细胞多能性。超级增强子(super-enhancers, SEs)是一种由连续排列的增强子调控元件串联形成的超长增强子簇,转录因子和协同因子大量富集于其上,可以强力驱动细胞相关基因的表达。SEs具有明显的细胞特异性,细胞中存在数百个SEs控制着关键基因,决定细胞命运走向【6】。 BAF作为一种染色体重组复合物,在干细胞多能性的维持和建立过程中都发挥着重要作用【7,8】。染色体在体细胞中往往结构相对紧密,而紧凑的位阻不利于转录因子的富集和基因的转录。在多能干细胞中需要大量增强子和多能性基因从紧凑的染色体上暴露出来以促进转录,这一过程需要BAF复合物发挥染色体重组的作用【9】。 在最新的这项研究中,研究团队经过深入的研究发现,BAF与YY1和OCT4蛋白在胚胎干细胞中相互作用以促进大量多能性基因的表达。BAF与YY1的相互作用一方面进一步加强了YY1的转录促进作用,另一方面,BAF的加入改变了YY1对多能性的调控机制,使得原本在多能性调控中YY1依赖的Myc通路转为依赖于Core通路(通过调控多能性基因Oct4、Nanog、Sall4等)。YY1、BAF和OCT4的相互作用使得该蛋白复合物不仅大量富集于启动子区域,还富集于超级增强子区域(下图),这也从另一方面验证了YY1的染色体结构蛋白的功能,暗示了YY1在多能干细胞中促进增强子启动子染色体三维互作的形成。参考文献 (References):1.    Vella,P., et al., Yin Yang 1 extends theMyc-related transcription factors network in embryonic stem cells. Nucleic Acids Res, 2012. 40(8): p. 3403-18.2.    Donohoe, M.E., et al., Targeted disruption of mouse Yin Yang 1 transcription factor results inperi-implantation lethality. Mol Cell Biol, 1999. 19(10): p. 7237-44.3.    Gordon, S., et al., Transcription factor YY1: structure, function, and therapeuticimplications in cancer biology. Oncogene, 2006. 25(8): p. 1125-42.4.    Wang, J., et al., A protein interaction network for pluripotency of embryonic stem cells.Nature, 2006. 444(7117): p. 364-8.5.    Weintraub, A.S., et al., YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell, 2017. 171(7):p. 1573-1588 e28.6.    Whyte, W.A., et al., Master transcription factors and mediator establish super-enhancers atkey cell identity genes. Cell, 2013. 153(2):p. 307-19.7.    Kadoch, C., et al., Proteomic and bioinformatic analysis of mammalian SWI/SNF complexesidentifies extensive roles in human malignancy. Nat Genet, 2013. 45(6): p. 592-601.8.    Singhal, N., et al., Chromatin-Remodeling Components of the BAF Complex FacilitateReprogramming. Cell, 2010. 141(6):p. 943-55.9.    Meshorer, E., et al., Hyperdynamic plasticity in pluripotent embryonic of chromatin proteinsstem cells. Developmental Cell, 2006. 10(1):p. 105-116.转载自BioArt

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Laboratory Culture实验室文化

Lab logo, “Ding Lab-STEM CELL”, represents the name and the research area of our lab. For the hollowed-out decorative pattern, from the left to right, are the  molecular formula of  sialic acid and the protein SOX2 interaction with chromatin, which are the typical  research project of our lab. The emotion using in the logo is the prof Ding commonly used. The emotion using here convy the encouragement, facing the reality optimistic and finishing the job profoundly. The element of our logo is coming from the ideal of pixel and writing brush, which represent the “wet experiment” and the “dry bioinformatics experiment”一、实验室LOGO设计文字:“Ding Lab – STEM CELL”,为实验室名称与研究方向。镂空部分的花纹:从左到右分别是唾液酸的分子式、SOX2的蛋白互作组和互作的染色质,为实验室具体研究内容的几个例子。图案:“”源于丁老师最常用的三个表情,代表实验室积极鼓励自己和他人、微笑面对现实、可靠完成工作的精神。字体:选用了柔顺的毛笔风和像素风,表现实验室既做实验也做生信。二、实验室活动Our lab also has the basketball game after the seminar, summer vacation activity, birthday party and the lantern festive party. 组会之后会有篮球赛活动:暑假集体出游活动:生日聚餐活动:元宵节福利:

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Postgraduate Teaching研究生教学

Our lab’s postgraduate education includes the daily scientific research training and the seminar reports. And the form contains individual conference, team work and mentor guiding. Seminar contains the usual seminar, team seminar and the stem cell union conference.本课题组的研究生教学包括日常科研技能训练和组会。其中日常科研训练包括个人会议、课题小组和导师指导。组会包括常规组会、小组会和干细胞联合组会。 一、Daily Scientific Research Training日常科研训练 1. Individual Conference个人会议Individual conference is to report the latest progress and paper reading to the Prof.Ding and looking forewords to the further work, one per week. 每周一次,向丁老师汇报上周课题进展与文献阅读情况,讨论下一步的工作安排。2. Project Group课题小组The team seminar is for the team member, which are doing the same project, the topic is based on what are doing, and focus on the difficult point. Our lab has six groups, which are reprogramming team, saccharides team, ABC team, wch team and bioinformation team.本课题组以小组为课题进行课题,组内成员共同学习、攻克课题难点。本课题组共有重编程小组、疾病模型小组、糖组、ABC小组、Wch小组和生信组六个小组。 3. Teacher Guiding导师指导Prof.ding also provide some guiding on specific points.课题中的关键实验或难点实验丁老师会亲自提供实验指导。二、Seminar组会 1. Usual Seminar常规组会The usual seminar of our lab starts at Saturday 1pm-7pm, every weekend. 3 main reporters will give us great view of our progress and the rencent science advance. 每周六13:00~19:00,三个演讲人分别汇报重要期刊中与本实验室方向相关的文献、课题工作进展和一篇精读文献的背景介绍。Part 1 is the cnsreports, each one should read the related aera, and transcrbted.Part 2 is work report, giving brief but profound working procedure of our recently doing. And the background, scientific question, solution ways, results display and critical thinking.Part 3 is paper reading report, the topic must be related to what you are doing.具体包括以下三个部分:CNS汇报:每人有自己负责的期刊,汇报要求覆盖所有文献,解释基本工作与创新点,重点讲解与课题组方向有关的工作。 工作汇报:以类似Seminar的形式汇报近期工作,包括背景、科学问题、解决方法、结果展示和个人思考。 文献汇报:每周选定一篇精读文献,汇报文献相关的研究背景和解析结果部分的难点,提出与本组课题相关的思考 2. 小组会 3D Seminar 3D小组会:The team seminar and 3d seminar are held respectly each week. The main purpose of this seminar is to teach student the knowledge of bioinformation by discussing, doing presentation and exchange the ideal.每两周一次,主要目的为生信分析人员与实验人员之间进行讨论,另外进行生信相关知识的教学普及,或者讨论3D相关的实验技术、想法或文献。 Tech Seminar技术小组会:The tech seminar is used to solve the idiographic question of technique during the experiment.每两周一次,与3D小组会间隔进行,主要讨论关键实验技术的原理和操作细节。 Seminar课题会:Once a week, the group reports on the progress of the project, discusses relevant literature and further work. The seminar will be held remotely with the collaborative research team.每周一次,小组内汇报课题进展、讨论相关文献和进一步工作。会与合作的课题组远程进行课题会。 3. Stem Cell United Conference干细胞联合组会The stem cell united conference is held twice a week, providing the lunch during the noon, which give the scientists a flexible time to chat, relax and get learned. The main reporters are form the research area of stem cell and medicen, meanwhile some experts would be asked to give a report too. And this conference provides the scientists a great chance to have cooperation.每两周一次,以午餐会的形式进行。干细胞与再生医学平台的实验室人员轮流进行课题汇报,也会邀请校外嘉宾作汇报,目的为促进各个课题组之间的交流合作。

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