Meister P, Mango SE, Gasser SMLocking the genome: nuclear organization and cell fate. Curr Opin Genet Dev 21:167-174

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Current opinion in genetics & development (Impact Factor: 7.57). 02/2011; 21(2):167-74. DOI: 10.1016/j.gde.2011.01.023
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The differentiation of pluripotent or totipotent cells into various differentiated cell types is accompanied by a restriction of gene expression patterns, alteration in histone and DNA methylation, and changes in the gross nuclear organization of eu- and heterochromatic domains. Several recent studies have coupled genome-wide mapping of histone modifications with changes in gene expression. Other studies have examined changes in the subnuclear positioning of tissue-specific genes upon transcriptional induction or repression. Here we summarize intriguing correlations of the three phenomena, which suggest that in some cases causal relationships may exist.

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    • "This is a very exciting hypothesis that promotes the concept of a direct mechanical link between chromatin dynamics and a canalized plasticity in genome expression, enabling the establishment of pluripotency or totipotency. The possibility that a loose or open nuclear architecture is progressively locked when embryonic cells progress towards their differentiated state has been proposed for animals (Meister et al., 2011) and plants (Costa and Shaw, 2007; Rosa et al., 2014). Moreover , recent studies in mouse early embryos clearly showed that the mobility of core histones in itself is inversely correlated with the transition from totipotency to pluripotency , and to lineage commitment (Boskovic et al., 2014). "
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    ABSTRACT: Sexual reproduction in flowering plants offers a number of remarkable aspects to developmental biologists. First, the spore mother cells -precursors of the plant reproductive lineage- are specified late in development as opposed to precocious germline isolation during embryogenesis in most animals. Second, unlike in most animals where meiosis directly produces gametes, plant meiosis entails the differentiation of a multicellular, haploid gametophyte within which gametic as well as non-gametic -accessory- cells are formed. These observations raise the question of the factors inducing but also the modus operandi of cell fate transitions that occur de novo in floral tissues and gametophytes, respectively. Cell fate transitions in the reproductive lineage imply cellular reprogramming appreciated at the physiological, cytological, transcriptome but also chromatin level. A number of observations point to large-scale chromatin reorganization events associated with cellular differentiation of the female spore mother cells and of the female gametes. Those include a reorganization of the heterochromatin compartment, genome-wide alteration of the histone modification landscape, remodeling of nucleosome composition. The dynamic expression of DNA methyltransferases and actors of small RNAs pathway also suggest additional, global epigenetic alterations that remain to be characterized. Are these events a cause or a consequence of cellular differentiation and how do they contribute to cell fate transition? Does chromatin dynamics induces competence for immediate cellular functions (meiosis, fertilization) or does it also contribute long-term effects in cellular identity and developmental competence of the reproductive lineage? This review attempts to review those fascinating questions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    The Plant Journal 05/2015; 83(1). DOI:10.1111/tpj.12890 · 5.97 Impact Factor
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    • "Events that occur in the context of chromatin, such as DNA replication, DNA repair or transcription, necessitate a constant remodelling of nucleosomes (2). Post-translational modifications (PTM) of core histones contribute to determining states of active and repressed chromatin that can be faithfully transmitted from one generation to the next (3). The discovery of variants of histone H3 that are enriched in PTMs associated with either active or repressed chromatin has led to the notion that histone variant exchange facilitates plasticity at the nucleosome level (4). "
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    ABSTRACT: The epigenome is defined as a type of information that can be transmitted independently of the DNA sequence, at the chromatin level, through post-translational modifications present on histone tails. Recent advances in the identification of histone 3 variants suggest a new model of information transmission through deposition of specific histone variants. To date, several non-centromeric histone 3 variants have been identified in mammals. Despite protein sequence similarity, specific deposition complexes have been characterized for both histone 3.1 (H3.1) and histone 3.3 (H3.3), whereas no deposition complex for histone 3.2 (H3.2) has been identified to date. Here, we identified human H3.2 partners by immunopurification of nuclear H3.2 complexes followed by mass spectrometry analysis. Further biochemical analyses highlighted two major complexes associated with H3.2, one containing chromatin associated factor-1 subunits and the other consisting of a subcomplex of mini chromosome maintenance helicases, together with Asf1. The purified complexes could associate with a DNA template in vitro.
    Nucleic Acids Research 01/2014; 42(6). DOI:10.1093/nar/gkt1355 · 9.11 Impact Factor
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    • "The nuclear periphery is a unique subcompartment of the nucleus that consists of the inner nuclear membrane (INM) and its associated proteins, nuclear lamina (NL) and chromatin [1,2]. A number of genes were found to preferentially localize to the nuclear periphery, and re-position upon transcription activation or cellular differentiation [3-5]. Nonetheless, how gene positioning to the nuclear periphery confers regulatory functions remains largely unclear. "
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    ABSTRACT: How gene positioning to the nuclear periphery regulates transcription remains largely unclear. By cell imaging, we have previously observed the differential compartmentalization of transcription factors and histone modifications at the nuclear periphery in mouse C2C12 myoblasts. Here, we aim to identify DNA sequences associated with the nuclear lamina (NL) and examine this compartmentalization at the genome-wide level. We have integrated high throughput DNA sequencing into the DNA adenine methyltransferase identification (DamID) assay, and have identified ~15, 000 sequencing-based Lamina-Associated Domains (sLADs) in mouse 3T3 fibroblasts and C2C12 myoblasts. These genomic regions range from a few kb to over 1 Mb and cover ~30% of the genome, and are spatially proximal to the NL. Active histone modifications such as H3K4me2/3, H3K9Ac and H3K36me3 are distributed predominantly out of sLADs, consistent with observations from cell imaging that they are localized away from the nuclear periphery. Genomic regions around transcription start sites of expressed sLAD genes display reduced association with the NL; additionally, expressed sLAD genes possess lower levels of active histone modifications than expressed non-sLAD genes. Our work has shown that genomic regions associated with the NL are characterized by the paucity of active histone modifications in mammalian cells, and has revealed novel connections between subnuclear gene positioning, histone modifications and gene expression.
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