Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions.
Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions.
复制标题
DOI：
10.1186/gb-2012-13-10-r91
复制
发表时间：
2012-10-03
期刊：
影响因子：
12.3
通讯作者：
Savenkova MI
中科院分区：
文献类型：
--
作者：
Skinner MK;Manikkam M;Haque MM;Zhang B;Savenkova MI
环境诱导的表观遗传跨代遗传成人发病的疾病涉及到各种表型的变化，表明在基因组活动的一般改变。对雄性和雌性F3代乙烯菌核利与对照谱系大鼠中不同组织转录组的研究表明，检查的所有组织均具有跨代转录组。将来自11种不同组织的微阵列与基因生物网络分析进行比较。虽然每个组织的跨代转录组是独特的，但在组织之间鉴定了共同的细胞途径和过程。聚类分析确定了具有协调基因表达的基因模块，并且每个基因模块都具有调节组织特异性基因表达和功能的独特基因网络。在男性和女性的基因组中发现了大量具有统计学显著性的过度表达基因簇。这些基因簇的大小范围为2-5兆碱基，其中许多基因簇对应于之前在精子中发现的表观突变，这些突变传递疾病表型的表观遗传跨代遗传。综合观察结果表明，所有来自表观遗传改变的生殖系的组织都发育有该组织特有的跨代转录组，但基因组中常见的表观遗传控制区域可能协调调节这些组织特异性转录组。这种系统生物学方法提供了深入了解各种成人发病疾病表型的表观遗传跨代遗传的分子机制。
Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes, suggesting a general alteration in genome activity. Investigation of different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had transgenerational transcriptomes. The microarrays from 11 different tissues were compared with a gene bionetwork analysis. Although each tissue transgenerational transcriptome was unique, common cellular pathways and processes were identified between the tissues. A cluster analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue-specific gene expression and function. A large number of statistically significant over-represented clusters of genes were identified in the genome for both males and females. These gene clusters ranged from 2-5 megabases in size, and a number of them corresponded to the epimutations previously identified in sperm that transmit the epigenetic transgenerational inheritance of disease phenotypes. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome may coordinately regulate these tissue-specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes.
登录
查看更多内容
DOI：
10.1073/pnas.0610410104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Crews, David;Gore, Andrea C.;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
DOI：
10.1016/j.bbagrm.2011.03.007
发表时间：
2011-08
影响因子：
4.7
作者：
Hauser, Marie-Theres;Aufsatz, Werner;Jonak, Claudia;Luschnig, Christian
通讯作者：
Luschnig, Christian
影响因子：
4
作者：
Delaval, K;Feil, R
通讯作者：
Feil, R
DOI：
10.1126/science.1190614
发表时间：
2010-10-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng S;Jacobsen SE;Reik W
通讯作者：
Reik W
影响因子：
7.2
作者：
Bartolomei, Marisa S;Ferguson-Smith, Anne C
通讯作者：
Ferguson-Smith, Anne C