简介：Arabidopsisthaliana嘘一deacetylase1(AtHD1或AtHDA19)，酵母RPD3的一个相当或相同的事物，是在植物的许多生理、发展的过程的一个全球管理者。尽管有为在植物基因规定和开发的AtHD1的一个角色的基因证据，AtHD1的生物化学、细胞的性质糟糕被理解。这里，我们在vivo报导AtHD1的细胞的本地化模式并且嘘在vitro的一项deacetylase活动。绿荧光灯的蛋白质(GFP)的短暂、稳定的表示在洋葱房间标注了AtHD1并且分别地，在转基因的Arabidopsis的根，种子和叶子表明AtHD1在euchromatic区域大概在原子核是局部性的并且从核排除。AtHD1的本地化模式与涉及核形成和transgenes的silencing并且分别地重复了DNA元素的AtHD2和AtHDA6的那些不同。另外，一hist一deacetylase活动试金证明在细菌生产的recombinantAtHD1示威了一特定嘘在vitro的一项deacetylase活动。数据建议AtHD1是原子蛋白质并且拥有嘘为对植物生长和开发重要的全球transcriptional规定负责的一项deacetylase活动。

简介：AbstractEpigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions, especially for controlling gene expression. Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies, including acute myeloid leukemia (AML). Epigenetic therapies, including hypomethylating agents (HMAs) and histone deacetylase (HDAC) inhibitors, were developed to reprogram the epigenetic abnormalities in AML. However, the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown. An overview of these epigenetic therapies is given here. A literature search was conducted through PubMed database, looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th, 2019. Various types of articles, including original research and reviews, were assessed, identified, and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients. We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone, the combination of epigenetic therapies with intensive chemotherapy, and the combination of both types of epigenetic therapies. Relevant clinical trials were also discussed. Generally speaking, the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous, and that HMAs combination regimens probably contribute to significant response rates. However, more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.

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简介：Objective:Therecurrenceorprogressionunderendocrinetherapyinhormonereceptor-positive(HR+)advancedbreastcancer(ABC)remainedacriticalclinicalchallenge.Chidamideisanoralsubtype-selectivehistonedeacetylase(HDAC)inhibitorwithmultiplefunctionsintumorgrowthinhibitionandmicroenvironmentmodulationviaepigeneticreprogramming.Thepurposeofthisstudywastoevaluatethesafety,pharmacokinetics(PK),andpreliminaryefficacyofchidamideincombinationwithexemestaneinHR+ABCpatients.Methods:EligiblepatientswerepostmenopausalwomenwithHR+ABCrecurrentorprogressedtoatleastoneendocrinetherapy.Bloodsampleswereobtainedintherun-inperiodandthefirstdayofcombinationtreatmentforPKanalysis.Incombinationtreatment,patientsweregivenexemestane25mgdailyandchidamide30mgtwiceaweek(BIW)untilprogressionofdiseaseorintolerabletoxicities.Atreatmentcyclewasdefinedas4weeks.Safety,PKparameters,andpreliminaryefficacywereevaluated.Results:Atotalof20patientswereenrolledbetweenJulyandDecember,2015.Themediannumberoftreatmentscyclewas5.2(20.8weeks)with2patientsstillontreatmentatthedatacut-offdateofOctober,2017.Thetreatment-relatedadverseevents(AE)≥grade3inmorethan2patientswereneutropenia(35%),thrombocytopenia(30%),andleucopenia(20%).Theplasmaexposureofexemestanewasconsistentinthepresenceorabsenceofchidamide.Aslightincreaseinchidamideexposurewasnotedinthepresenceofexemestane,probablyduetotheinter-andintra-patientvariations.Thebestresponsein16evaluablepatientswasassessedbyResponseEvaluationCriteriainSolidTumors(RECIST),including4patientswithpartialresponse,10patientswithstabledisease.Themedianprogression-freesurvival(PFS)was7.6months.Conclusions:ThecombinationofchidamidewithexemestanewasgenerallywelltoleratedwithpromisingpreliminaryefficacyinHR+ABCpatients.Theoverallresultsfromthisstudyencouragefurtherpivotaltrialinthispatie

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简介：Hearinglossisoneofthemostfrequenthealthissuesinindustrializedcountries.Thepathogenesisandmolecularmechanismsofhearinglossarestillunclear.Histonedeacetylases(HDACs)areemergingaskeyenzymesinmanyphysiologicalprocesses,includingchromatinremodeling,regulationoftranscription,DNArepair,metabolism,genomestabilityandproteinsecretion.RecentstudiesindicatedthatHDACsareassociatedwiththedevelopmentandprogressionofhearingloss.DysfunctionofHDACscouldpromotetheoxidativestressandagingintheinnerear.Inlightofconsideringthecurrentstagnationinthedevelopmentoftherapeuticoptions,theneedfornewstrategiesinthetreatmentofhearinglosshasneverbeensopressing.Inthisreview,wewillsummarizethereportedliteraturesforHDACsinhearinglossanddiscusshowHDACfamilymembersshowdifferentperformancesforthepossibilityofprocessofdiseasesdevelopment.Thepossibilityofpharmacologicalinterventiononhearinglossopensanovelpathinthetreatmentofhearingloss.

简介：MicroRNAs(miRNA)指导在基因表示的一个重要角色在植物为到环境条件的发展进程和回答要求了的顺序特定的posttranscriptional基因silencing玩。然而，很少对transcriptional和miRNA表示的posttranscriptional规定被知道。Histoneacetylation在染色质改变起一个重要作用并且为基因激活被要求。由在Arabidopsis的异种分析miRNAs和相应主要miRNAs的子集的累积，我们显示出那histoneacetyltransferaseGCN5(一般控制非镇压的protein5)在miRNA上有一般压抑的效果生产，当它为一个子集的表示被要求时(例如压力可诱导)MIRNA基因。在miRNA生产的GCN5的一般否定功能多半通过象DICERLIKE1(DCL1)那样的miRNA机械基因的间接压抑被完成，有锯齿(SE)，偏下性的LEAVES1(HYL1)和ARGONAUTE1(AGO1)。染色质immunoprecipitation试金表明GCN5指向到MIRNA基因的一个子集并且为在这些loci的histoneH3离氨酸14的acetylation被要求。而且，由trichostatin的histonedeacetylation的抑制一个处理或在histonedeacetylase，基因异种损害了某些miRNAs的累积。这些数据一起建议ArabidopsisGCN5在transcriptional和posttranscriptional层次防碍miRNA小径，histoneacetylation/deacetylation是涉及miRNA的规定的epigenetic机制生产。

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简介：组蛋白甲基化是参予细胞的过程的一个多样的数组的重要epigenetic现象并且被发现了与癌症被联系。几的Recentidentification嘘一demethylases证明了那嘘一甲基化是一个可逆过程。通过一条候选人途径，我们化学上有简历作为H3K27demethylase识别了JMJD3。进HeLa房间的JMJD3的Transfection引起了整齐的乙醇H3K27的特定的减小，但是没在di-和单音的甲基H3K27上有效果，或嘘H3K4和H3K9上的一离氨酸methylations。Theenzymatic活动要求JmjC域和被建议了为余因子绑定重要的保存组氨酸。试管内生物化学的实验证明那JMJD3directly催化demethylation。另外，我们发现JMJD3起来在前列腺癌症，和它的表示调整了在变形前列腺癌症是更高的。因此，我们作为能够把整齐的乙醇组从移开的ademethylase识别了JMJD3嘘一H3离氨酸27并且起来在前列腺癌症调整了。

简介：组蛋白deacetylases(HDAC)并且嘘一乙酰转移ases(帽子)是其酶的活动控制蛋白质离氨酸残余的乙酰化状态的二抵抗酶家庭，尤其是在核心histones.Acetylation的N终端扩展包含的那些嘘通过它对染色质符合构造的影响影响基因表示。Inaddition，几non-histone蛋白质由特定的离氨酸残余的乙酰化状态在他们的稳定性或生物功能被调整。HDAC在大量的生物学过程干涉并且是部分一多每个成员在有它的专业化功能的蛋白质家庭。另外，HDAC活动紧通过指向的招募，protein-proteininteractions和translational以后修正被控制。房间周期前进，房间幸存和区别的控制在这些酶的最重要的角色之中。因为这些过程被恶意的转变影响，HDAC禁止者作为反被开发在癌症病人的肿瘤的药和areshowing鼓励功效。

简介：Humanp100proteinconsistsoffourrepeateddomainsofstaphylococcalnuclease(SN)-likedomain,aswellasatudor(TD)domainthereafter.WehavepreviouslyshownthattheSN-likedomainofp100interactedwithSTAT6andthelargesubunitofRNApolII,resultingintheenhancementofSTAT6-mediatedgenetranscriptionalactivation.Here,weshowthatSN-likedomainalsointeractedwithCREBbindingprotein(CBP)anddirectlyenhancedtheacetyltransferaseactivityofCBPonhistone.Ontheotherhand,overexpressionofCBPalonehadnoabilitytosignificantlyincreaseSTAT6dependenttranscriptionalactivation,however,togetherwithp100protein,sufficientlyenhancedtheactivationoftranscriptionwhichwasinlinewiththepreviousresultthatp100proteinbridgedSTAT6withCBP.

简介：客观多重骨髓瘤是从B淋巴细胞发源的一种恶意的血浆房间疾病并且分泌monoclonal免疫球蛋白的大数量。它仍然目前是倔强的疾病之一。众多的研究证明在histoneacetylation的不平衡和多重骨髓瘤的occurance之间有一种集中的关系。这里，我们在增长，apoptosis，histoneH3和H4acetylation和histonedeacetylase的表示上调查了triptolide(TPL)的效果8(HDAC8)在vitro，探索它的反骨髓瘤机制。RPMI8226的生长上的triptolide的效果被3-(4,5-Dimethyl-2-thiazolyl)学习的方法-2,5-diphenyl-2H-tetrazolium(MTT)试金。Apoptosis被染色的Hoechst33258检测。acetyl-histoneH3和H4的蛋白质表情被西方的污点决定，并且HDAC8的表示被RT-PCR，西方的污点和共焦的显微镜学估计。结果Triptolide禁止了RPMI8226的增长并且在一个时间依赖者和剂量依赖者举止导致了apoptosis。36hIC50价值是(105.370敢漠?摀畲獧吗？

简介：ToexplorethemolecularmechanismofchromatinremodelinginvolvedintheregulationoftranscriptionalactivationofspecificgenesbyamyogenicregulatoryfactorMyogenin,weusedNIH3T3fibroblastswithastablyintegratedH1.1-GFPfusionproteintomonitorhistoneH1movementdirectlybyfluorescencerecov-eryafterphotobleaching(FRAP)inlivingcells.TheobservationfromFRAPexperimentswithmyogenintransfectedfibroblastsshowedthattheexchangerateofhistoneH1inchromatinwasobviouslyincreased,indicatingthatforcedexpressionofexogenousMyogenincaninducechromatinremodeling.Thehyper-acetylationofhistonesH3andH4frommyogenintransfectedfibroblastswasdetectedbytriton-acid-urea(TAU)/SDS(2-D)electrophoresisandWesternblotwithspecificantibodiesagainstacetylatedN-terminiofhistonesH3andH4.RT-PCRanalysisindicatedthatthenAChRa-subunitgenewasexpressedinthetrans-fectedfibroblasts.TheseresultssuggestthattheexpressionofexogenousMyogenincaninducechromatinremodelingandactivatethetranscriotionofMvogenin-targetedgeneinnon-musclecells.

简介：瞄准：检验在精子DNA损坏和精子之间的关系原子嘘染色的(H2B)。方法：我们从14连续asthenoteratozoospermic评估了精子样品不肥沃的人和六连续肥沃的控制。精子原子嘘染色的(H2B)和精子染色质正直(由精子染色质结构试金估计了并且表示了使用(i)DNA破碎索引的百分比[%DFI]并且(ii)高DNA污点能力[%HDS)])被评估。结果：HistoneH2B免疫细胞化学表明了二个原子染色模式：(i)焦点的有小斑点的染色；并且(ii)扩散染色。不肥沃的人有展出弥漫的H2B染色比的精子的一个更高吝啬的百分比做了肥沃的人(7.7%±4.6%vs.1.6%±1.2%，分别地P<0.01)。我们观察了在精子的比例之间的重要关系与弥漫原子嘘一染色和两精子%DFI(r=0.63，P<0.01)并且精子%HDS(r=0.63，P<0.01)。结论：数据证明不肥沃的人有精子的一个更高的比例与弥漫嘘一H2B与做肥沃的人并且建议精子DNA损坏力量比，至少部分地，由于反常地高嘘一个H2B层次。

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简介：Thelackofefficientandnon-toxicgenedelivery,preferablywithnon-viralDNAvectors,isgenerallyregardedasamajorlimitationforgenetherapy.Inthisstudy,awheathistoneH4genewasclonedfromTriticumaestivum,sequenced,modifiedandexpressedinE.coli.ThewheathistoneH4geneandreconstructedH4TLgeneencodedwheathistoneH4andarecombinantproteinof141aminoacidswithanapproximatemolecularweightof15500.GelelectrophoresismobilityshiftassaysdemonstratedthatthepurifiedproteinhadhighaffinityforDNA.Mostsignificantly,thecomplexofplasmidpEGFP/C1withH4TLwastransfectedwithincreasedefficiencyintoMCF-7,HO8910,LNCap,A549andHeLacellsinvitro.Theseresultsdemonstratethatthetargetingofnon-viralvectorstotumor-specificreceptorsprovidesacheap,simpleandhighlyefficienttoolforgenedelivery.

简介：除了DNA顺序信息，地点特定嘘一修正是在一个真核细胞的有机体的基因表示的另一个重要决定因素。我们选择了四个修正地点在普通嘘被知道显著地影响染色质功能并且产生的单音同种细胞或认出每那些地点特定的修正的polyclonal抗体。我们使用了这些抗体证明地点特定嘘一个修正层次在一样的有机体的不同机关仍然保持相对不变。我们也比较了层次选择嘘在几个代表性的有机体之中的一修正并且发现地点特定的修正在不同有机体之中是高度可变的，提供新卓见进进化分叉特定嘘一修正。

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