Distinctive Chromatin in Human Sperm Packages Genes that Guide Embryo Development
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15594 | GEO | 2009/06/15
SECONDARY ACCESSION(S): PRJNA115605
REPOSITORIES: GEO
Similar Datasets
Project description: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.
| S-EPMC2858064 | biostudies-literature
Project description:As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions to embryo development appear limited. However, our genome-wide approaches find nucleosomes at low levels genome-wide, but also significantly enriched at imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of other developmental transcription and signaling factors. Developmental promoters were often DNA hypomethylated, and bore histone modifications localized to discrete locations: H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX loci, certain non-coding RNAs, and generally to paternally-expressed imprinted loci. In contrast, H3K4me3 is generally absent at paternally-repressed imprinted loci. Interestingly, repressive H3K27me3 is enriched at many developmental promoters that lack early expression in embryos, with significant overlap with bivalent (H3K4me3/H3K27me3) promoters in ES cells. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators. *Use of ChIP-seq to identify regions enriched for histone, and several histone variants in human sperm. *Histone Localization: Chromatin was prepared from 40 million sperm as described previously (1) in the absence of crosslinking reagent, treated with sequential and increasing MNase (10U-160U), and centrifuged to sediment protamine-associated DNA, releasing mononucleosomes. The pooled mononucleosomes were gel purified (~140-155 bp) for sequencing and array analysis. Mononucleosomes for ChIP-seq were sequenced from a single donor (3 replicas combined) or a donor pool (4 donors each ~6 million reads) and data was normalized to 20 million input control reads (pooled donor sperm genomic DNA). *Chromatin IP and Preparation for Genomics Methods: ChIP methods were as described previously (2) but were performed without a cross linking agent and slight modifications to the salt levels, 250 mM NaCl, 200 mM LiCl, and replaced the TE wash with 150 mM PBS wash. A subset of the modifications H3K4me3, H3K27me3 and H2A.z were done from a donor pool and only analyzed by Solexa. Each IP was repeated three time and the three replicas were pooled. For sequencing, DNA lengths corresponding to mononucleosomes with adapters (220-280 bp) were gel purified after the addition of the Illumina adaptors. The sequencing data was normalized to histone donor pool (D1 was subsampled to 5million and combined with the reads from D2-D4). 1. Zalenskaya, I.A., Bradbury, E.M. & Zalensky, A.O. Chromatin structure of telomere domain in human sperm. Biochem Biophys Res Commun 279, 213-8 (2000). 2. Gordon, M. et al. Genome-Wide Dynamics of SAPHIRE, an Essential Complex for Gene Activation and Chromatin Boundaries. Mol Cell Biol 27, 4058-69 (2007). Samples corresponding to each GSE15690_Seq* processed data supplementary file: GSE15690_Seq_H2AZ.txt: GSM392695 GSE15690_Seq_H3K27Me3.txt: GSM392699, GSM392700 GSE15690_Seq_H3K4Me3.txt: GGSM392696-GSM392698 GSE15690_Seq_HistoneMnase_D1.txt: GSM392701-GSM392707, GSM392714-GSM392716 GSE15690_Seq_HistoneMnase_PooledDonor.txt: GSM392708-GSM392713, GSM392717-GSM392720
2009-06-15 | E-GEOD-15690 | biostudies-arrayexpress
Project description:As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions to embryo development appear limited. However, our genome-wide approaches find nucleosomes at low levels genome-wide, but also significantly enriched at imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of other developmental transcription and signaling factors. Developmental promoters were often DNA hypomethylated, and bore histone modifications localized to discrete locations: H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX loci, certain non-coding RNAs, and generally to paternally-expressed imprinted loci. In contrast, H3K4me3 is generally absent at paternally-repressed imprinted loci. Interestingly, repressive H3K27me3 is enriched at many developmental promoters that lack early expression in embryos, with significant overlap with bivalent (H3K4me3/H3K27me3) promoters in ES cells. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.
2009-06-15 | GSE15701 | GEO
Project description:As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions to embryo development appear limited. However, our genome-wide approaches find nucleosomes at low levels genome-wide, but also significantly enriched at imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of other developmental transcription and signaling factors. Developmental promoters were often DNA hypomethylated, and bore histone modifications localized to discrete locations: H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX loci, certain non-coding RNAs, and generally to paternally-expressed imprinted loci. In contrast, H3K4me3 is generally absent at paternally-repressed imprinted loci. Interestingly, repressive H3K27me3 is enriched at many developmental promoters that lack early expression in embryos, with significant overlap with bivalent (H3K4me3/H3K27me3) promoters in ES cells. Taken together, epigenetic marking in sperm is extensive, and correlated with developmental regulators.
2009-06-15 | GSE15690 | GEO
Project description:In mature human sperm, genes of importance for embryo development (i.e., transcription factors) lack DNA methylation and bear nucleosomes with distinctive histone modifications, suggesting the specialized packaging of these developmental genes in the germline. Here, we explored the tractable zebrafish model and found conceptual conservation as well as several new features. Biochemical and mass spectrometric approaches reveal the zebrafish sperm genome packaged in nucleosomes and histone variants (and not protamine), and we find linker histones high and H4K16ac absent, key factors that may contribute to genome condensation. We examined several activating (H3K4me2/3, H3K14ac, H2AFV) and repressing (H3K27me3, H3K36me3, H3K9me3, hypoacetylation) modifications/compositions genome-wide and find developmental genes packaged in large blocks of chromatin with coincident activating and repressing marks and DNA hypomethylation, revealing complex "multivalent" chromatin. Notably, genes that acquire DNA methylation in the soma (muscle) are enriched in transcription factors for alternative cell fates. Remarkably, whereas H3K36me3 is located in the 3' coding region of heavily transcribed genes in somatic cells, H3K36me3 is present in the promoters of "silent" developmental regulators in sperm, suggesting different rules for H3K36me3 in the germline and soma. We also reveal the chromatin patterns of transposons, rDNA, and tDNAs. Finally, high levels of H3K4me3 and H3K14ac in sperm are correlated with genes activated in embryos prior to the mid-blastula transition (MBT), whereas multivalent genes are correlated with activation at or after MBT. Taken together, gene sets with particular functions in the embryo are packaged by distinctive types of complex and often atypical chromatin in sperm.
| S-EPMC3065705 | biostudies-literature
Project description:We previously demonstrated that MnCl2 induces double-stranded DNA breaks in sperm in a process that we term as sperm chromatin fragmentation. Here, we tested if the levels of double-stranded DNA breaks were corelated to the concentration of MnCl2, and we compared this to another agent that causes single-stranded DNA breaks, H2O2. We found that both methods have the advantage of inducing DNA breaks in a concentration-dependent manner. Mouse sperm were treated with varying concentrations of either H2O2 or MnCl2, and the DNA damage was assessed by pulse-field gel electrophoresis, and the alkaline and neutral comet assays. Oocytes were injected with either treated sperm and the resulting embryos analyzed with an embryoscope to detect subtle changes in embryonic development. We confirmed that H2O2 treatment induced primarily single-stranded DNA breaks and MnCl2 induced primarily double-stranded DNA breaks, indicating different mechanisms of damage. These sperm were injected into oocytes, and the development of the resulting embryos followed with an embryoscope equipped with time lapse recording. We found that aberrations in early embryonic development by day 2 with even the lowest levels of DNA damage and that the levels of embryonic aberrations correlated to the concentration of either H2O2 or MnCl2. Low levels of H2O2 caused significantly more aberrations in embryonic development than low levels of MnCl2 even though the levels of DNA damage as measured by comet assays were similar. These data demonstrate that even low levels of sperm DNA damage cause delays and arrests in embryonic development.
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