Chromatin condensation but not DNA integrity of pig sperm is greater in the sperm-rich fraction

Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo development.In some mammals,like pigs,ejaculates are emitted in three separate fractions:pre-sperm,sperm-rich(SRF)and post sperm-rich(PSRF).These fractions are known to vary in volume,sperm concentration and quality,as well as in the origin and composition of seminal plasma(SP),with differences being also observed within the SRF one.Yet,whether disparities in the DNA integrity and chromatin condensation and pro-tamination of their sperm exist has not been interrogated.Results This study determined chromatin protamination(Chromomycin A3 test,CMA_(3)),condensation(Dibromobi-mane test,DBB),and DNA integrity(Comet assay)in the pig sperm contained in the first 10 m L of the SRF(SRF-P1),the remaining portion of the sperm-rich fraction(SRF-P2),and the post sperm-rich fraction(PSRF).While chromatin protamination was found to be similar between the different ejaculate fractions(P>0.05),chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF(P=0.018 and P=0.004,respectively).Regarding DNA integrity,no differences between fractions were observed(P>0.05).As the SRF-P1 has the highest sperm concentra-tion and ejaculate fractions are known to differ in antioxidant composition,the oxidative stress index(OSi)in SP,calcu-lated as total oxidant activity divided by total antioxidant capacity,was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF(0.42±0.06 vs.0.23±0.09 and 0.08±0.00,respectively;P<0.01);this index,in addition,was observed to be correlated to the sperm concentration of each fraction(Rs=0.973;P<0.001).Conclusion While sperm DNA integrity was not found to differ between ejaculate fractions,SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the PSRF.This could be related to the OSi of each fraction.

Targeting the chromatin structural changes of antitumor immunity

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Dek219 encodes the DICER-LIKE1 protein that affects chromatin accessibility and kernel development in maize

Chromatin accessibility plays a vital role in gene transcriptional regulation.However,the regulatory mechanism of chromatin accessibility,as well as its role in regulating crucial gene expression and kernel development in maize(Zea mays)are poorly understood.In this study,we isolated a maize kernel mutant designated as defective kernel219(dek219),which displays opaque endosperm and embryo abortion.Dek219 encodes the DICER-LIKE1(DCL1)protein,an essential enzyme in mi RNA biogenesis.Loss of function of Dek219 results in significant reductions in the expression levels of most mi RNAs and histone genes.Further research showed that the Heat shock transcription factor17(Hsf17)-Zm00001d016571 module may be one of the factors affecting the expression of histone genes.Assay results for transposase-accessible chromatin sequencing(ATAC-seq)indicated that the chromatin accessibility of dek219 is altered compared with that of wild type(WT),which may regulate the expression of crucial genes in kernel development.By analyzing differentially expressed genes(DEGs)and differentially accessible chromatin regions(ACRs)between WT and dek219,we identified 119 candidate genes that are regulated by chromatin accessibility,including some reported to be crucial genes for kernel development.Taken together,these results suggest that Dek219 affects chromatin accessibility and the expression of crucial genes that are required for maize kernel development.

Construction of a transposase accessible chromatin landscape reveals chromatin state of repeat elements and potential causal variant for complex traits in pigs

Background:A comprehensive landscape of chromatin states for multiple mammalian tissues is essential for elucidating the molecular mechanism underlying regulatory variants on complex traits.However,the genome-wide chromatin accessibility has been only reported in limited tissue types in pigs.Results:Here we report a genome-wide landscape of chromatin accessibility of 20 tissues in two female pigs at ages of 6 months using ATAC-seq,and identified 557,273 merged peaks,which greatly expanded the pig regulatory ele-ment repository.We revealed tissue-specific regulatory elements which were associated with tissue-relevant biologi-cal functions.We identified both positive and negative significant correlations between the regulatory elements and gene transcripts,which showed distinct distributions in terms of their strength and distances from corresponding genes.We investigated the presence of transposable elements(TEs)in open chromatin regions across all tissues,these included identifications of porcine endogenous retroviruses(PERVs)exhibiting high accessibility in liver and homology of porcine specific virus sequences to universally accessible transposable elements.Furthermore,we prior-itized a potential causal variant for polyunsaturated fatty acid in the muscle.Conclusions:Our data provides a novel multi-tissues accessible chromatin landscape that serve as an important resource for interpreting regulatory sequences in tissue-specific and conserved biological functions,as well as regula-tory variants of loci associated with complex traits in pigs.

Can the Prediction of Intrauterine Insemination Results by Used Aniline Blue Stain (ABS) and Sperm Chromatin Dispersion (SCD) Levels?

Introduction: This study aimed to perform routine seminal fluid analysis, sperm DNA fragmentation, and sperm function tests at the chromatin maturation level and evaluate pregnancy in the patients passing intrauterine insemination before starting Intrauterine Insemination (IUI) method. Materials and Methods: In this prospective study, 111 couples who underwent Intrauterine Insemination (IUI) in unexplained infertility patients were admitted to Al-Farah IVF and assisted reproductive center in Baghdad, Iraq between November 2020 and February 2021 were evaluated. Semen fluid analysis was performed based on (WHO 4th) guiding rules. In addition, Sperm Chromatin Dispersion (halo test) and sperm maturation were performed with Aniline Blue Stain (ABS). Results: Sperm Chromatin Dispersion (SCD) groups were compared in terms of pregnancy outcome;the positive pregnancy rate was found to be above in the normal SCD groups (p = 0.0005). In addition, Aniline Blue Stain (ABS) groups were compared in the terms of pregnancy outcome;the positive pregnancy rate was found to be higher in the normal ABS group (p = 0.017). Conclusion: Our study showed that the use of DNA fragmentation (SCD) and sperm maturation tests (ABS) together with routine semen analysis in intrauterine insemination cases will make a significant contribution to the prediction of Intrauterine Insemination (IUI) increased results. So, these results indicate a defect in the effect of DNA fragmentation on the outcome of intrauterine insemination.

Chicken chromatin accessibility atlas accelerates epigenetic annotation of birds and gene fine-mapping associated with growth traits

The development of epigenetic maps, such as the ENCODE project in humans, provides resources for gene regulation studies and a reference for research of disease-related regulatory elements. However,epigenetic information, such as a bird-specific chromatin accessibility atlas, is currently lacking for the thousands of bird species currently described.The major genomic difference between birds and mammals is their shorter introns and intergenic distances, which seriously hinders the use of humans and mice as a reference for studying the function of important regulatory regions in birds. In this study, using chicken as a model bird species, we systematically compiled a chicken chromatin accessibility atlas using 53 Assay of Transposase Accessible Chromatin sequencing(ATAC-seq)samples across 11 tissues. An average of 50 ?796open chromatin regions were identified per sample,cumulatively accounting for 20.36% of the chicken genome. Tissue specificity was largely reflected by differences in intergenic and intronic peaks, with specific functional regulation achieved by two mechanisms: recruitment of several sequence-specific transcription factors and direct regulation of adjacent functional genes. By integrating data from genome-wide association studies, our results suggest that chicken body weight is driven by different regulatory variants active in growth-relevant tissues. We propose CAB39L(active in the duodenum), RCBTB1(muscle and liver), and novel long non-coding RNA ENSGALG00000053256(bone) as candidate genes regulating chicken body weight. Overall, this study demonstrates the value of epigenetic data in fine-mapping functional variants and provides a compendium of resources for further research on the epigenetics and evolution of birds and mammals.

中年男性精子DNA碎片率对体外受精-胚胎移植妊娠结局的影响

目的探讨中年男性精子DNA碎片率(DFI)与精液质量和体外受精-胚胎移植妊娠结局的关系。方法共收集180例接受常规体外受精-胚胎移植治疗且男性年龄>38岁的精液标本。根据DFI的阈值分成(<30%和≥30%)两组。主要测量指标包括:常规精液参数、激素水平、DFI、受精率、优质胚胎率、临床妊娠率等。结果通过比较分析发现,DFI与男性卵泡刺激素(FSH)、精子活力、精子形态密切相关,且精子活力随着DFI水平的升高而下降(P<0.05);当DFI≥30%时,优质胚胎率下降(P<0.05),但两组的临床妊娠率差异无显著性(P>0.05)。结论DFI可以作为中年男性精液常规分析的重要参考指标,虽然DFI影响优质胚胎率,但与辅助生殖治疗的临床妊娠结局无关。

活性依赖性神经保护蛋白在肿瘤中的研究进展

活性依赖性神经保护蛋白(ADNP)是一种转录因子。近些年来研究发现,ADNP具有染色质重塑、细胞周期与增殖调控、DNA损伤与修复、细胞运动与转移、化疗耐药等肿瘤相关生物学功能,在多种肿瘤中均存在不同程度的突变及异常表达,与肿瘤的发生、发展密切相关。本文综述了ADNP的分子结构、功能特点及其在多种肿瘤发生、发展中的研究进展,旨在为肿瘤的诊治研究方向提供新思路。

西藏地区结直肠癌免疫治疗和靶向治疗相关分子标志物的检测及意义

目的研究西藏地区结直肠癌中SWI/SNF相关、基质相关、肌动蛋白依赖性染色质调节因子A亚科成员4(SMARCA4)/Brahma相关基因1、V-raf鼠类肉瘤病毒癌基因同源物B(BRAF)、P53、程序性死亡受体1(PD-1)及程序性死亡配体1(PD-L1)免疫组织化学表达和BRAF、神经营养因子酪氨酸受体激酶(NTRK)基因改变情况,为西藏地区结直肠癌患者的靶向治疗及免疫治疗提供依据。方法收集2015年1月至2021年7月西藏自治区人民医院经手术切除病理确诊为结直肠癌病例64例,全部病例均进行SMARCA4、BRAF、P53、PD-1、PD-L1免疫组织化学染色和NTRK1、NTRK2、NTRK3融合基因荧光原位杂交检测及BRAF V600E基因突变PCR检测。结果64例结直肠癌病例男女比例1.21∶1,平均年龄(56.59±13.27)岁;46例(71.88%)位于结肠,18例(28.12%)位于直肠;60例(93.75%)为腺癌,4例(6.25%)为其他类型;11例(17.19%)为T1或T2期,53例(82.81%)为T3或T4期;24例(37.50%)出现淋巴结转移。免疫组织化学方面,64例中1例(1.56%)SMARCA4部分肿瘤细胞表达减弱或缺失,4例(6.25%)BRAF肿瘤细胞阳性表达,35例(54.69%)P53为突变型表达;45例(70.31%)PD-1肿瘤相关免疫细胞阳性比例分数<10%,19例(29.69%)≥10%;52例(81.25%)PD-L1联合阳性分数<10,12例(18.75%)≥10。64例NTRK1、NTRK2、NTRK3融合基因检测均为阴性;4例(6.25%)检测到BRAF V600E基因突变;1例SMARCA4表达缺失病例未检测到SMARCA4基因改变。PD-L1的表达与错配修复缺陷/高度微卫星不稳定和PD-1的高表达呈显著正相关(χ^(2)=10.223,P=0.001;χ^(2)=11.979,P=0.001)。结论西藏地区结直肠癌中较少出现SMARCA4表达减弱或缺失及NTRK融合基因改变,少数病例有BRAF V600E基因突变,Pan-TRK和BRAF免疫组织化学可作为NTRK融合基因及BRAF基因突变的初筛方法。错配修复缺陷/高度微卫星不稳定的病例中更容易出现PD-L1蛋白高表达,这部分患者有望获益于免疫治疗。P53突变与PD-L1表达无相关性,PD-1的高表达和PD-L1的高表达呈正相关。

染色质调节因子对乳腺癌预后的预测价值

目的探讨染色质调节因子(CRs)在乳腺癌中的差异表达及其对预后的预测价值。方法利用癌症基因组图谱数据库筛选乳腺癌和正常乳腺组织中差异表达的CRs,并通过最小绝对值收敛和选择算子算法-Cox回归分析构建预后风险模型,根据风险分数(Risk score)将乳腺癌患者分为高风险组和低风险组;同时分析风险模型与乳腺癌患者临床特征的相关性,并对每个基因进行单独验证。结果本研究识别了127个在乳腺癌中差异表达的CRs,并基于16个关键CRs构建了预后风险模型;低风险组患者中年龄≤65岁、StageⅠ~Ⅱ期、Ⅲ~Ⅳ期、T_(0)~T_(1)、T_(2)~T_(3)、N_(0)~N_(1)、N_(2)~N_(3)者总生存期均高于高风险组(均P<0.05)。结论CRs能预测乳腺癌患者的预后。

精子染色质完整性对功能的影响及其检测方法研究进展

精子染色质不仅携带父系DNA等遗传信息,还携带有结构蛋白、表观遗传信息、高级染色质结构(如基质附着区和端粒)等众多信息,这些信息在胚胎发育过程中均发挥着重要作用。本文主要综述了精子染色质携带的这些不同信息对精子功能和胚胎发育的影响及其相关检测方法的研究进展,以期为临床不育、胚胎停育和反复流产的病因筛查提供理论依据和科学的诊疗策略,改善自然受孕和辅助生殖助孕的妊娠结局。

Osteonectin促进骨髓来源间充质干细胞成骨分化的机制及其与青少年特发性脊柱侧凸的相关性研究

目的 探究Osteonectin在促进骨髓间充质干细胞(BMSCs)成骨分化的分子机制,以及Osteonectin在青少年特发性脊柱侧凸(AIS)中的作用。方法 将2020年5月—2022年5月就诊的20例AIS及健康体检20例分别作为AIS组和健康组。使用qRT-PCR技术测定2组BMSCs中Osteonectin、BMP2以及Wnt/β-catenin信号通路相关基因(Tcf7、Lef1)和成骨分化相关基因(Runx2、Osteocalcin)的表达水平。通过X线检测AIS患者的Cobb角度,并分析上述基因表达水平与Cobb角度的相关性。在BMSCs中,加入Osteonectin和BMP2抑制剂Noggin,并分为对照组、Osteonectin组和Osteonectin+Noggin组。通过qRT-PCR检测BMSCs中BMP2、Tcf7、Lef1、Runx2和Osteocalcin mRNA表达水平。采用ChIP-qPCR检测β-catenin在Runx2和Osteocalcin基因转录起始位(TSS)的富集水平。结果 与健康组比较,AIS组BMSCs中Osteonectin、BMP2、Tcf7、Lef1、Runx2和Osteocalcin mRNA表达水平均降低(P<0.05);Osteonectin、BMP2、Tcf7、Lef1、Runx2和Osteocalcin mRNA表达水平与AIS患者Cobb角度呈负相关(r=-0.466 3、-0.369 1、-0.272 7、-0.543 4、-0.606 5、-0.343 3,P<0.05,P<0.01)。与对照组比较,Osteonectin组BMSCs中BMP2、Tcf7、Lef1、Runx2和Osteocalcin mRNA表达水平升高,且β-catenin在Runx2和Osteocalcin mRNA TSS富集水平增加(P<0.05)。相比Osteonectin组,Osteonectin+Noggin组BMSCs中Tcf7、Lef1、Runx2和Osteocalcin mRNA表达水平降低,β-catenin在Runx2和Osteocalcin mRNA TSS富集水平降低(P<0.05)。结论 在AIS患者中,BMSCs中Osteonectin、BMP2-Wnt/β-catenin的表达以及成骨分化水平与AIS疾病的发展呈负相关。Osteonectin通过激活BMP2-Wnt/β-catenin信号通路,促使β-catenin转录激活成骨分化相关基因,从而促进BMSCs的成骨分化。

脱氧核糖鸟苷酸对染色质松弛程度的调控作用

真核生物的染色质结构在基因转录、DNA修复等生物学过程中发生动态变化,其松弛程度和组蛋白修饰受到多种机制的严密调控.在研究DNA修复机制的过程中,发现敲除S期抑制基因(Spd1)可以逆转多种DNA损伤应答(DDR)突变体的表型缺陷,该遗传相互作用涉及到DDR的多个信号转导通路.Spd1的主要功能是抑制脱氧核糖核苷酸(dNTP)的生物合成,这说明敲除Spd1可以通过改变dNTP库的水平或组分来影响DNA损伤应答.进一步分析发现,Spd1缺陷促进染色质松弛,导致突变菌株的染色质对微球菌核酸酶的敏感,由此说明dNTP水平的增高可以促进染色质的紧密程度.最后,通过利用可以转运外源dNTP的FY2317菌株,制备原生质体,利用半离体的体系证明过量的dNTP,特别是脱氧核糖鸟苷酸(dGTP)可以模拟Spd1缺失菌株的表型,显著提高染色质的松弛程度.综上所述,研究发现了一种新的调控染色质松弛程度的遗传机制,可以影响DNA损伤修复的应答.

湖羊lncRNA-269的鉴定及转录调控分析

[目的]本文旨在研究湖羊长链非编码RNA-269(long no-coding RNA-269,lncRNA-269)序列特征、表达模式和转录调控,为后续开展lncRNA-269的功能研究提供理论基础。[方法]以湖羊为研究对象,采用5′/3′RACE结合PCR扩增方法获得其序列全长,利用RT-qPCR方法鉴定其在湖羊组织中的表达模式,并利用PCR方法扩增其启动子区,鉴定其启动子区特征,分析其转录调控情况。[结果]湖羊lncRNA-269全长3 146 bp,组织表达谱显示其在湖羊各组织中广泛表达,且在健康卵泡中显著高表达,其表达水平与NR5A1 mRNA水平和血清中雌二醇(E_(2))水平呈正相关。荧光素酶活性分析发现在lncRNA-269启动子区的-359~-17 nt有1个转录激活基序,在-1 485~-942 nt有1个转录抑制基序。JASPAR软件预测发现在lncRNA-269转录抑制启动子区域存在FOXO3、PDX1等转录因子结合位点,在转录激活区域有SMAD4、YY1等转录因子结合位点。过表达SMAD4可显著提升lncRNA-269启动子区荧光素酶活性,染色质免疫沉淀(ChIP)-PCR试验进一步确认了SMAD4特异性与lncRNA-269启动子区结合。[结论]湖羊lncRNA-269在健康卵泡中显著高表达,其启动子区存在一个转录激活区域和一个转录抑制区域,转录因子SMAD4可通过与lncRNA-269启动子区结合显著上调lncRNA-269的启动子活性。

谷子SWI3基因鉴定及其在盐和干旱胁迫下的表达分析

SWI/SNF染色质重塑因子在植物的生长发育及逆境应答过程中起重要作用。本研究首先通过序列比对,从谷子基因组中鉴定出6个候选SiSWI3基因,分别命名为SiSWI3A、SiSWI3B、SiSWI3C1、SiSWI3C2、SiSWI3D1和SiSWI3D2。然后对上述基因的结构、编码蛋白、启动子元件、亚细胞定位等进行生物信息学分析和预测,结果表明:SiSWI3蛋白都含有SANT Motif,且亚细胞定位预测显示SiSWI3成员主要被定位在细胞核中;SiSWI3基因启动子区域含有大量与光响应、激素类应答、逆境应答、代谢调控等相关的顺式作用元件。最后采用实时荧光定量PCR(qRT-PCR)检测这些基因在谷子苗期盐胁迫和干旱胁迫下的表达量变化,检测结果表明:SiSWI3基因受盐和干旱不同程度的诱导,说明SiSWI3基因参与谷子苗期盐胁迫和干旱胁迫应答。本研究所得结论为进一步探究SiSWI3染色质重塑因子在抗逆作物谷子的逆境响应中的功能和机制奠定了基础。

染色质三维构象在精子发生中的研究进展

染色质是调节生物体遗传的重要物质,是维持细胞有序表达基因及蛋白质的重要载体。随着科学技术的不断进步,许多研究通过染色质构象捕获技术(High-Through Chromosome Conformation Capture,Hi-C)对染色质内部结构进行解析,对染色质区室、染色质疆域等有了更清晰的认识。在哺乳动物的精子发生过程中,染色质结构的改变对基因调控等起到了重要作用。精子发生是精原细胞增殖分化形成精子的过程,包括精原细胞的自我更新与分化、精母细胞的减数分裂以及精细胞的变形。本文主要阐述染色质三维构象捕获技术及其衍生技术、染色质的层级结构、精子发生过程中染色质三维构象变化的前沿进展,为精子发生的机制研究提供新思路。

真核细胞DNA复制的多层级调控

DNA复制是生命体最基础的代谢过程。在人细胞中,数千个DNA复制源在染色质环境下被同时激活,共同起始DNA复制过程并完成基因组的拷贝。复制过程有组织地进行,既受到染色质环境的约束和调控,又需协调与其他DNA代谢事件的关系,以保证基因组DNA和表观遗传信息准确且稳定地继承。随着研究技术的发展和研究数据的积累,系统性、整体性地研究真核细胞,尤其是哺乳动物细胞,在复杂染色质环境下的DNA复制是未来的研究趋势。本文将从多个角度总结真核DNA复制在染色质环境中的多层级调控模式,期望为今后的研究带来启示。

基于生物信息学筛选肠易激综合征免疫浸润下的染色质调节因子

目的:通过生物信息学分析,筛选出肠易激综合征(irritable bowel syndrome, IBS)免疫浸润下的潜在染色质调控因子(chromatin regulators, CRs),并阐述其与免疫细胞、免疫功能之间的联系。方法:整合CRs文件和IBS基因表达矩阵,进行加权基因共表达分析和差异性分析,取其交集CRs;基于交集CRs,进行蛋白质-蛋白质相互作用(protein-protein interaction, PPI)分析并构建网络图;利用基因表达矩阵进行免疫浸润的提取和量化,分析免疫细胞之间和免疫功能之间的相关性和差异性,并与PPI网络图中的CRs进行相关性分析;构建风险模型,分析与免疫浸润密切相关的CRs的风险概率,从而筛选出潜在的CRs。结果:PPI分析共确定13个IBS中存在相互作用的CRs;免疫细胞中,B细胞与滤泡辅助性T细胞的相关系数值最高,呈正相关(r=0.90);免疫功能中,检查点与T细胞共抑制的相关系数值最高,呈正相关(r=0.89);与健康受试者相比,IBS患者树突状细胞、未成熟树突状细胞、Th1细胞和抗原呈递共刺激显著增高(P均<0.05);CRs与免疫浸润相关性分析结果显示,SIN3转录调节因子家族成员B(SIN3B)与自然杀伤细胞呈正相关,丝氨酸/精氨酸重复基质蛋白2(SRRM2)与Th1细胞、抗原呈递共刺激呈正相关,而DPY30与辅助性T细胞、Th1细胞呈负相关;风险模型结果显示,SIN3B、SRRM2可能是IBS的独立风险因素。结论:SIN3B、SRRM2为IBS免疫浸润的潜在CRs,其可能通过调控自然杀伤细胞、Th1细胞和抗原呈递共刺激,从而调节IBS的发生发展。

三维基因组学在神经精神疾病领域的研究进展

神经精神疾病影响着全球数千万人的生活,成为日益严重的社会问题。遗传是介导神经精神疾病发生的重要因素之一。但是,人群全基因组关联研究(genome-wide association studies, GWAS)检测出的疾病风险位点大多位于基因组的非编码区域,是目前进一步鉴定疾病风险基因及推动发病机制研究的瓶颈所在。三维基因组学(three-dimensional genomics)关注染色质空间构象及基因组序列的远程相互作用,相关技术的开发和应用为建立疾病风险位点与靶向基因间的关联提供直接证据,拓展了疾病风险基因的鉴定。与此同时,疾病风险位点与基因相互作用的细胞特异性为理解疾病的发生机制提供了全新思路。最后,染色质空间构象重塑可调控集群基因的转录表达,可能参与介导疾病的表型复杂性及异质性。本文在简单介绍三维基因组学的基础概念和应用的基础上,重点总结及分析其在神经精神疾病领域的研究进展,主要包括精神分裂症(schizophrenia, SCZ)、阿尔茨海默病(Alzheimer's disease, AD)和孤独症谱系障碍(autism spectrum disorder, ASD),为相关疾病的发病机制研究提供新思路。

哺乳动物合子基因激活时期染色体的表观遗传学变化

哺乳动物受精后,胚胎由母源因子调控逐渐转变为合子型调控,表达合子转录本,即合子基因激活(zygotic gene activation,ZGA)。其间发生了剧烈的表观遗传学变化,如组蛋白修饰、DNA甲基化重编程以及染色质重塑等。表观遗传学重塑的异常可导致严重的发育缺陷,甚至胚胎致死。因此,了解ZGA过程中的表观遗传学变化对于明确其致病机制至关重要。本文综述了哺乳动物合子基因激活时期DNA甲基化重编程、组蛋白修饰以及染色质重塑3个方面的最新研究进展,以期为深入探究哺乳动物合子基因激活时期染色体的表观遗传变化提供参考。