For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
101
views
23
references
 Top references
cited by
158
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      328
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Distinctive Chromatin in Human Sperm Packages Genes for Embryo Development

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          As nucleosomes are widely replaced by protamine in mature human sperm, epigenetic contributions of sperm chromatin to embryo development have been considered highly limited. However, we find the retained nucleosomes significantly enriched at loci of developmental importance including imprinted gene clusters, miRNA clusters, HOX gene clusters, and the promoters of stand-alone developmental transcription and signaling factors. Importantly, histone modifications localize to particular developmental loci. H3K4me2 is enriched at certain developmental promoters, whereas large blocks of H3K4me3 localize to a subset of developmental promoters, regions in HOX clusters, certain non-coding RNAs, and generally to paternally-expressed imprinted loci, but not paternally-repressed loci. Notably, H3K27me3 is significantly enriched at developmental promoters that are repressed in early embryos, including many bivalent (H3K4me3/H3K27me3) promoters in embryonic stem cells. Finally, 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.

          Related collections

          Most cited references23

          • Record: found
          • Abstract: found
          • Article: not found

          In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state.

          Marius Wernig, Alexander Meissner, Ruth Foreman … (2007)
          Nuclear transplantation can reprogramme a somatic genome back into an embryonic epigenetic state, and the reprogrammed nucleus can create a cloned animal or produce pluripotent embryonic stem cells. One potential use of the nuclear cloning approach is the derivation of 'customized' embryonic stem (ES) cells for patient-specific cell treatment, but technical and ethical considerations impede the therapeutic application of this technology. Reprogramming of fibroblasts to a pluripotent state can be induced in vitro through ectopic expression of the four transcription factors Oct4 (also called Oct3/4 or Pou5f1), Sox2, c-Myc and Klf4. Here we show that DNA methylation, gene expression and chromatin state of such induced reprogrammed stem cells are similar to those of ES cells. Notably, the cells-derived from mouse fibroblasts-can form viable chimaeras, can contribute to the germ line and can generate live late-term embryos when injected into tetraploid blastocysts. Our results show that the biological potency and epigenetic state of in-vitro-reprogrammed induced pluripotent stem cells are indistinguishable from those of ES cells.
          Article 0 comments Cited 529 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA.

            Steen Ooi, Chen Qiu, Emily Bernstein … (2007)
            Mammals use DNA methylation for the heritable silencing of retrotransposons and imprinted genes and for the inactivation of the X chromosome in females. The establishment of patterns of DNA methylation during gametogenesis depends in part on DNMT3L, an enzymatically inactive regulatory factor that is related in sequence to the DNA methyltransferases DNMT3A and DNMT3B. The main proteins that interact in vivo with the product of an epitope-tagged allele of the endogenous Dnmt3L gene were identified by mass spectrometry as DNMT3A2, DNMT3B and the four core histones. Peptide interaction assays showed that DNMT3L specifically interacts with the extreme amino terminus of histone H3; this interaction was strongly inhibited by methylation at lysine 4 of histone H3 but was insensitive to modifications at other positions. Crystallographic studies of human DNMT3L showed that the protein has a carboxy-terminal methyltransferase-like domain and an N-terminal cysteine-rich domain. Cocrystallization of DNMT3L with the tail of histone H3 revealed that the tail bound to the cysteine-rich domain of DNMT3L, and substitution of key residues in the binding site eliminated the H3 tail-DNMT3L interaction. These data indicate that DNMT3L recognizes histone H3 tails that are unmethylated at lysine 4 and induces de novo DNA methylation by recruitment or activation of DNMT3A2.
            Article 0 comments Cited 448 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors.

              Fabio Mohn, Michael Weber, Michael Rebhan … (2008)
              Cellular differentiation entails loss of pluripotency and gain of lineage- and cell-type-specific characteristics. Using a murine system that progresses from stem cells to lineage-committed progenitors to terminally differentiated neurons, we analyzed DNA methylation and Polycomb-mediated histone H3 methylation (H3K27me3). We show that several hundred promoters, including pluripotency and germline-specific genes, become DNA methylated in lineage-committed progenitor cells, suggesting that DNA methylation may already repress pluripotency in progenitor cells. Conversely, we detect loss and acquisition of H3K27me3 at additional targets in both progenitor and terminal states. Surprisingly, many neuron-specific genes that become activated upon terminal differentiation are Polycomb targets only in progenitor cells. Moreover, promoters marked by H3K27me3 in stem cells frequently become DNA methylated during differentiation, suggesting context-dependent crosstalk between Polycomb and DNA methylation. These data suggest a model how de novo DNA methylation and dynamic switches in Polycomb targets restrict pluripotency and define the developmental potential of progenitor cells.
              Article 0 comments Cited 290 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 0410462
                Journal ID (pubmed-jr-id): 6011
                Journal ID (nlm-ta): Nature
                Title: Nature
                ISSN (Print): 0028-0836
                ISSN (Electronic): 1476-4687
                Publication date Nihms-submitted: 26 January 2010
                Publication date (Electronic): 14 June 2009
                Publication date (Print): 23 July 2009
                Publication date PMC-release: 21 April 2010
                Volume: 460
                Issue: 7254
                Pages: 473-478
                Affiliations
                [1 ] Howard Hughes Medical Institute, Department of Oncological Sciences, and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112
                [2 ]IVF and Andrology Laboratories, Departments of Surgery, Obstetrics and Gynocology, and Physiology. University of Utah School of Medicine, Salt Lake City, Utah 84112
                [3 ]Research Informatics and Bioinformatics Core Facility, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112
                Author notes

                Author Contributions. B.R.C., D.T.C. and S.S.H.; overall design. D.T.C. and S.S.H.: acquisition of samples, clinical logistics, patient consenting, Institutional Review Board documents. B.R.C., S.S.H., D.A.N. and H.Z.; detailed molecular and genomics approaches. D.A.N.; data processing and array analysis. S.S.H. and D.A.N.; sequencing analysis. S.S.H.; experiments and figures. J.P.; immunoblotting and bisulphite sequencing. B.R.C. wrote the manuscript.

                Article
                Manuscript ID: hhmipa120193
                DOI: 10.1038/nature08162
                PMC ID: 2858064
                PubMed ID: 19525931
                SO-VID: d64b6845-1328-438c-a971-7880e878d90c
                History
                Funding
                Funded by: Howard Hughes Medical Institute
                Award ID: ||HHMI_
                Categories
                Subject: Article

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content328

                See all similar

                Cited by385

                See all cited by

                Most referenced authors853

                See all reference authors