细胞重编程中的表观遗传分子机制

成体细胞可以通过核移植、细胞融合或者特定因子导入的方式实现重编程回到多能性状态。在重编程的过程中,表观遗传水平的调控机制起到了非常关键的作用。通过回顾重编程的研究进展来探讨表观遗传学在重编程中的调控机制。     

副突变及其表观遗传机制的研究进展

经典遗传学的研究方法为许多遗传性疾病和遗传相关性疾病的预防、诊断和治疗提供了在分子水平上的直接线索,然而人类疾病的遗传表现始终存在着经典遗传学法则所不能解释的现象。副突变(paramutation)是上世纪50年代首次在玉米中发现的一种非孟氏遗传模式,其传递的等位基因不存在核苷酸序列的差异,提示了表观遗传机制可能参与了基因表达和表型的可遗传变化。近期的研究发现关于副突变现象的解释可能涉及一种新的表观遗传学调控机制,即由RNA(特别是非编码RNA)引发的基因组改变参与了副突变的发生和维持。其中DNA甲基转移酶II所介导的RNA甲基化发挥了极其重要的作用。对副突变及其机制的研究不仅能够深化人类对遗传和生命本质的认识,还有助于开拓在生物工程和疾病诊疗等应用领域的新思路。本文综述了副突变的分子机制和研究进展,并且探讨了副突变在疾病研究和基因治疗中的应用前景。     

“表观遗传机制、技术及应用”学术研讨会在京召开

为了交流“表观遗传学”的前沿研究成果,探讨表观遗传学领域的新技术和新方法以及我国表观遗传学研究的发展战略,由中国科学院生命科学与生物技术局、中国科学院人事教育局、中国遗传学会主办,中国科学院心理研究所行为遗传学中心、     

表观遗传修饰在糖脂代谢中的作用

表观遗传学是研究没有DNA序列变化的、可遗传的基因表达改变。表观遗传修饰可以参与多种生命过程,其在糖脂代谢中也发挥了重要的作用。生物体内的糖脂代谢关系密切,糖脂代谢紊乱会导致多种代谢性疾病的发生。文章主要从DNA甲基化、组蛋白修饰、非编码RNA调控等方面综述了表观遗传修饰在糖脂代谢中的研究进展。     

中国南北方汉族人群DNA甲基化表观遗传差异研究

目的 族群地域、体貌特征等表型是基因型与环境共同作用的结果。大量基因组学研究表明,汉族人群具有混合特征,内部存在明显的南北遗传差异。本研究旨在探索研究表观基因组在中国南北方汉族人群之间是否存在差异,并筛选差异遗传位点。方法 使用GLINT软件对483份汉族样本的全基因组甲基化芯片数据进行EWAS分析,使用Lasso回归方法筛选位点。使用多元逻辑回归算法构建南北方汉族人群预测模型,通过十折交叉验证的方法评估。结果 筛选出一组南北方汉族之间差异显著的CpG位点,准确性为99.03%,Kappa系数为0.979 6。结论 本研究表明南北方汉族人群之间存在表观遗传差异,本研究为进一步开展不同地域汉族人群之间的表观遗传差异研究奠定了基础。     

早期负性经历的表观遗传学研究进展

表观遗传学(epigenetics)是指不涉及DNA序列改变、可以通过有丝分裂和减数分裂进行遗传的基因表达变化的遗传学分支领域。目前研究主要集中在DNA甲基化、组蛋白密码、染色质重塑和非编码RNA调控等方面。早期负性经历是指个体出生早年所经历的不良生活事件,还包括个体出生前所经历的负性生活事件。大量研究表明早期负性经历对个体成年后的行为会造成明显影响。本文将综述早期负性经历中表观遗传的各种机制。     

表观遗传修饰在学习和记忆中的调节作用

学习和记忆行为是大脑的基本功能,它使得生物个体能够更好地适应环境的变化。揭示学习和记忆的分子生物学机制是现代神经生物学发展的目标之一。经过近40年的研究现已初步证实了突触可塑性在学习和记忆中所起的关键作用。而近年来的研究发现,表观遗传修饰对学习和记忆过程具有重要的调控作用。这一发现将有利于进一步揭示学习和记忆的复杂机制,并将为某些认知障碍性疾病的治疗提供新的思路。     

早期负性经历的表观遗传学研究进展

表观遗传学（epigenetics）是指不涉及DNA序列改变、可以通过有丝分裂和减数分裂进行遗传的基因表达变化的遗传学分支领域。目前研究主要集中在DNA甲基化、组蛋白密码、染色质重塑和非编码RNA调控等方面。早期负性经历是指个体出生早年所经历的不良生活事件,还包括个体出生前所经历的负性生活事件。大量研究表明早期负性经历对个体成年后的行为会造成明显影响。本文将综述早期负性经历中表观遗传的各种机制。     

孕期营养不良影响子代生长发育的表观遗传机制

表观遗传学是一门研究核酸序列不变,基因的可遗传变化的表达和调控的遗传学分支学科,主要包括DNA甲基化、组蛋白共价修饰、染色质重塑、基因沉默和RNA调控等机制。近年来,表观遗传修饰的检测方法也逐渐完善。营养物质不仅构成生命体的物质基础,还可以通过表观遗传调控机制对生命体的代谢活动进行一定的调节。由于早期胚胎和哺乳期幼仔产后早期所需营养物质全部和部分来源于母体孕期营养,因此本文综述了母体孕期营养水平对后代生长发育的表观遗传调节机制——DNA甲基化和组蛋白修饰。     

Emergent roles of maternal microchimerism in postnatal development

Maternal microchimerism (MMc) is the phenomenon that a low number of cells from the mother persists within her progeny. Despite their regular presence in mammalian pregnancies, the overall cell type repertoire and roles of maternal cells, especially after birth, remain unclear. By using transgenic mouse strains and human umbilical blood samples, recent studies have for the first time characterized and quantified MMc cell type repertoires in offspring, identified the cross-generational influence on fetal immunity, and determined possible factors that affect their presence in offspring. This review summarizes new findings, especially on the maternal cell type repertoires and their potential role in utero, in postnatal life, and long after birth.     

The influence of maternal care in shaping human survival and fertility

The influence of maternal care on child survival has evolved throughout human history due to variation in altriciality, allocare, and maternal behaviors. Here, we study the impact of these factors on the force of selection acting on age-specific survival and fertility (measured with elasticity analysis) in a model that incorporates the dependence of child survival on maternal survival. Results reveal life-history changes that cannot be elucidated when considering child's survival independent of maternal survival: decrease of late fertility and increase of late survival, and concomitant decrease of early and late fertility. We also show that an increase of child altriciality in early humans might explain the main human life-history traits: a high life expectancy and postreproductive life; a long juvenile period and a higher, and narrowed, fertility at the peak of the reproductive period.     

Arginine vasopressin 1a receptor gene and maternal behavior: evidence of association and moderation

This study examined associations among maternal sensitivity, mothers' early adversity and the Arginine Vasopressin 1a Receptor (AVPR1A) gene. Early adversity in mothers' background has been found to be associated with lower maternal sensitivity. Animal literature suggests that variation in the AVPR1A gene is associated with parenting quality. The goal of the study was to examine the role of the AVPR1A gene in maternal sensitivity, especially under conditions of high early adversity. Participants included 151 Caucasian women from a community sample. The women were videotaped in their home while interacting separately with two of their children (target child = 18 months, older sibling <6 years). Evidence was found for an association between the AVPR1A gene and maternal sensitivity. Mothers with two copies of the long RS3 alleles were less sensitive than mothers with one or zero copies of the long alleles. This association was strongest under conditions of high maternal early adversity.     

Sex differences in life history drive evolutionary transitions among maternal,paternal, and bi‐parental care

Evolutionary transitions among maternal, paternal, and bi‐parental care have been common in many animal groups. We use a mathematical model to examine the effect of male and female life‐history characteristics (stage‐specific maturation and mortality) on evolutionary transitions among maternal, paternal, and bi‐parental care. When males and females are relatively similar – that is, when females initially invest relatively little into eggs and both sexes have similar mortality and maturation – transitions among different patterns of care are unlikely to be strongly favored. As males and females become more different, transitions are more likely. If females initially invest heavily into eggs and this reduces their expected future reproductive success, transitions to increased maternal care (paternal → maternal, paternal → bi‐parental, bi‐parental → maternal) are favored. This effect of anisogamy (i.e., the fact that females initially invest more into each individual zygote than males) might help explain the predominance of maternal care in nature and differs from previous work that found no effect of anisogamy on the origin of different sex‐specific patterns of care from an ancestral state of no care. When male mortality is high or male egg maturation rate is low, males have reduced future reproductive potential and transitions to increased paternal care (maternal → paternal, bi‐parental → paternal, maternal → bi‐parental) are favored. Offspring need (i.e., low offspring survival in the absence of care) also plays a role in transitions to paternal care. In general, basic life‐history differences between the sexes can drive evolutionary transitions among different sex‐specific patterns of care. The finding that simple life‐history differences can alone lead to transitions among maternal and paternal care suggests that the effect of inter‐sexual life‐history differences should be considered as a baseline scenario when attempting to understand how other factors (mate availability, sex differences in the costs of competing for mates) influence the evolution of parental care.     

Effects of maternal nutrient restriction during early or mid-gestation without realimentation on maternal physiology and foetal growth and development in beef cattle

The aim of this study is to determine the effects of early and mid-gestation nutrient restriction on maternal metabolites and foetal growth. Primiparous Angus cows were synchronized and inseminated with semen from one sire. Dietary treatments were: control to gain 1 kg/week (CON) or 0.55% maintenance energy and CP requirements (nutrient restricted; NR). A subset of dams was fed NR (n=8) or CON (n=8) from days 30 to 110 of gestation. Another group was fed CON (n=8), days 30 to 190; NR (n=7), days 30 to 110 followed by CON days 110 to 190; or CON, (n=7) days 30 to 110 followed by NR days 110 to 190. Cows were harvested at days 110 or 190 of gestation, when foetal measurements and samples were collected. Cows that were NR during days 30 to 110 or 110 to 190 of gestation lost significant BW and body condition score (P<0.001), this was associated with reduced plasma glucose during NR (P<0.002). Foetal weights, empty foetal weights, abdominal and thoracic circumferences were all reduced (P<0.03) in day 110 NR animals. Foetal perirenal adipose as a percentage of empty foetal weight was increased (P=0.01) in NR day 110 female foetuses compared with CON foetus. Maternal serum triglycerides at day 110 of gestation were decreased (P<0.05) in NR dams, whereas foetal serum triglycerides were increased (P<0.05) in response to maternal NR. Foetal weights tended to be reduced (P=0.08) in NR/CON and CON/NR v. CON/CON cattle at day 190 of gestation. Empty foetal weights, abdominal and thoracic circumferences were reduced (P⩽0.03) in NR/CON and CON/NR v. CON/CON cattle. Brain weight as a percentage of empty foetal weight was increased (P<0.001) in NR/CON and CON/NR v. CON/CON cattle. Foetal perirenal adipose as a percentage of empty foetal weight was increased (P=0.003) in NR/CON and CON/NR v. CON/CON cattle. Maternal serum triglycerides at day 190 of gestation were decreased (P<0.05) in association with maternal NR. Foetal serum triglycerides at day 190 of gestation were increased (P<0.05) in response to maternal NR during early gestation but decreased by NR in mid gestation compared with CON foetuses. The data show that maternal nutrient restriction during early or mid-gestation cause’s asymmetrical foetal growth restriction, regardless if the restriction is preceded or followed by a period of non-restriction.     

Determining the adaptive potential of maternal stress

Ecological and medical researchers are investing great effort to determine the role of Maternally‐Derived Stress (MDS) as an inducer of phenotypic plasticity in offspring. Many researchers have interpreted phenotypic responses as unavoidable negative outcomes (e.g., small birth weight, high anxiety); however, a biased underestimate of the adaptive potential of MDS‐induced effects is possible if they are not viewed within an ecologically relevant or a life‐history optimization framework. We review the ecological and environmental drivers of MDS, how MDS signals are transferred to offspring, and what responses MDS induces. Results from four free‐living vertebrate systems reveals that although MDS induces seemingly negative investment trade‐offs in offspring, these phenotypic adjustments can be adaptive if they better match the offspring to future environments; however, responses can prove maladaptive if they unreliably predict (i.e., are mismatched to) future environments. Furthermore, MDS‐induced adjustments that may prove maladaptive for individual offspring can still prove adaptive to mothers by reducing current reproductive investment, and benefitting lifetime reproductive success. We suggest that to properly determine the adaptive potential of MDS, researchers must take a broader integrated life‐history perspective, appreciate both the immediate and longer term environmental context, and examine lifetime offspring and maternal fitness.     

Parental influence on early development in the European sea bass

Fertilization, survival during incubation and hatching were highly correlated and strongly influenced by the female parent and the interaction between both parents of the sea bass Dicentrarchus labrax. A single significant male effect was detected on hatching and may reflect a genetic component determining survival from fertilization to hatching. Egg size and total length of 8-day-old larvae (age of first feeding) were also subjected to the influence of the female but the two parameters were not correlated. A significant interaction between both parents was also observed for length of larvae. The survival rates were significantly correlated in two consecutive years indicating that reproductive performances may be repeatable. Although the effect of the male parent on early sea bass development is shown for the first time, it seems that most of the parental effects on early performance in this species are due to females even when hormonal stimulations are performed at very close prematurational stages of oocyte development.     

Intergenerational effects of maternal birth season on offspring size in rural Gambia

Environmental conditions experienced in early life can influence an individual's growth and long-term health, and potentially also that of their offspring. However, such developmental effects on intergenerational outcomes have rarely been studied. Here we investigate intergenerational effects of early environment in humans using survey- and clinic-based data from rural Gambia, a population experiencing substantial seasonal stress that influences foetal growth and has long-term effects on first-generation survival. Using Fourier regression to model seasonality, we test whether (i) parental birth season has intergenerational consequences for offspring in utero growth (1982 neonates, born 1976-2009) and (ii) whether such effects have been reduced by improvements to population health in recent decades. Contrary to our predictions, we show effects of maternal birth season on offspring birth weight and head circumference only in recent maternal cohorts born after 1975. Offspring birth weight varied according to maternal birth season from 2.85 to 3.03 kg among women born during 1975-1984 and from 2.84 to 3.41 kg among those born after 1984, but the seasonality effect reversed between these cohorts. These results were not mediated by differences in maternal age or parity. Equivalent patterns were observed for offspring head circumference (statistically significant) and length (not significant), but not for ponderal index. No relationships were found between paternal birth season and offspring neonatal anthropometrics. Our results indicate that even in rural populations living under conditions of relative affluence, brief variation in environmental conditions during maternal early life may exert long-term intergenerational effects on offspring.