Distinctive chromatin in human sperm packages genes for embryo development
Saher Sue Hammoud,David A. Nix,Haiying Zhang,Jahnvi Purwar,Douglas T. Carrell,Bradley R. Cairns +5 more
TLDR
It is shown that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX genes clusters, and the promoters of stand-alone developmental transcription and signalling factors.Abstract:
Because nucleosomes are widely replaced by protamine in mature human sperm, the epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. Here we show that the retained nucleosomes are significantly enriched at loci of developmental importance, including imprinted gene clusters, microRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signalling factors. Notably, histone modifications localize to particular developmental loci. Dimethylated lysine 4 on histone H3 (H3K4me2) is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain noncoding RNAs, and generally to paternally expressed imprinted loci, but not paternally repressed loci. Notably, trimethylated H3K27 (H3K27me3) is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Furthermore, developmental promoters are generally DNA hypomethylated in sperm, but acquire methylation during differentiation. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.read more
Citations
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Missing heritability and strategies for finding the underlying causes of complex disease
Evan E. Eichler,Jonathan Flint,Greg Gibson,Augustine Kong,Suzanne M. Leal,Jason H. Moore,Joseph H. Nadeau +6 more
TL;DR: Seven leading geneticists offer their opinion about where the 'missing heritability' of complex diseases might be found, what this could tell us about the underlying genetic architecture of common diseases and how this could inform research strategies for uncovering genetic risk factors.
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Epigenetics and the environment: emerging patterns and implications.
TL;DR: Although the underlying mechanisms remain largely unknown, particularly in humans, mechanistic insights are emerging from experimental model systems, which have implications for structuring future research and understanding disease and development.
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Transgenerational Epigenetic Inheritance: myths and mechanisms
TL;DR: Although the inheritance of epigenetic characters can certainly occur-particularly in plants-how much is due to the environment and the extent to which it happens in humans remain unclear.
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Epigenetic reprogramming in plant and animal development.
TL;DR: The mechanisms of genome-wide erasure of DNA methylation, which involve modifications to 5-methylcytosine and DNA repair, are being unraveled.
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Paternally Induced Transgenerational Environmental Reprogramming of Metabolic Gene Expression in Mammals
Benjamin R. Carone,Lucas Fauquier,Naomi Habib,Jeremy M. Shea,Caroline E. Hart,Ruowang Li,Christoph Bock,Christoph Bock,Chengjian Li,Hongcang Gu,Phillip D. Zamore,Alexander Meissner,Alexander Meissner,Zhiping Weng,Hans A. Hofmann,Nir Friedman,Oliver J. Rando +16 more
TL;DR: It is indicated that parental diet can affect cholesterol and lipid metabolism in offspring and define a model system to study environmental reprogramming of the heritable epigenome.
References
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Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
Journal ArticleDOI
Statistical significance for genomewide studies
John D. Storey,Robert Tibshirani +1 more
TL;DR: This work proposes an approach to measuring statistical significance in genomewide studies based on the concept of the false discovery rate, which offers a sensible balance between the number of true and false positives that is automatically calibrated and easily interpreted.
Journal ArticleDOI
A comparison of normalization methods for high density oligonucleotide array data based on variance and bias
TL;DR: Three methods of performing normalization at the probe intensity level are presented: a one number scaling based algorithm and a method that uses a non-linear normalizing relation by comparing the variability and bias of an expression measure and the simplest and quickest complete data method is found to perform favorably.
Journal ArticleDOI
A Bivalent Chromatin Structure Marks Key Developmental Genes in Embryonic Stem Cells
Bradley E. Bernstein,Tarjei S. Mikkelsen,Tarjei S. Mikkelsen,Xiaohui Xie,Michael Kamal,Dana J. Huebert,James Cuff,Ben Fry,Alexander Meissner,Marius Wernig,Kathrin Plath,Rudolf Jaenisch,Alexandre Wagschal,Robert Feil,Stuart L. Schreiber,Stuart L. Schreiber,Eric S. Lander,Eric S. Lander +17 more
TL;DR: It is proposed that bivalent domains silence developmental genes in ES cells while keeping them poised for activation, highlighting the importance of DNA sequence in defining the initial epigenetic landscape and suggesting a novel chromatin-based mechanism for maintaining pluripotency.
Journal ArticleDOI
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.