Chromatin signatures of pluripotent cell lines

Azuara, Véronique; Perry, Pascale; Sauer, Stephan P. A.; Spivakov, Mikhail; Jørgensen, Helle F.; Roshan, John; Gouti, Mina; Casanova, Miguel; Warnes, Gary; Merkenschlager, Matthias; Fisher, Amanda G.

doi:10.1038/ncb1403

Cited by 1,227 publications

(1,205 citation statements)

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“…Recent studies have documented distinctive properties of nuclear architecture and chromatin structure in stem cells (Azuara et al, 2006;Bernstein et al, 2006;Meshorer and Misteli, 2006). These characteristics of stemness may not be compatible with an effective decatenation checkpoint; in other words, it is possible that stem cells cannot simultaneously maintain multipotency and the decatenation checkpoint.…”

Section: Why a Deficiency In Stem And Progenitor Cells?mentioning

confidence: 99%

The decatenation checkpoint

Damelin

Bestor

2007

Br J Cancer

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The decatenation checkpoint delays entry into mitosis until the chromosomes have been disentangled. Deficiency in or bypass of the decatenation checkpoint can cause chromosome breakage and nondisjunction during mitosis, which results in aneuploidy and chromosome rearrangements in the daughter cells. A deficiency in the decatenation checkpoint has been reported in lung and bladder cancer cell lines and may contribute to the accumulation of chromosome aberrations that commonly occur during tumour progression. A checkpoint deficiency has also been documented in cultured stem and progenitor cells, and cancer stem cells are likely to be derived from stem and progenitor cells that lack an effective decatenation checkpoint. An inefficient decatenation checkpoint is likely to be a source of the chromosome aberrations that are common features of most tumours, but an inefficient decatenation checkpoint in cancer stem cells could also provide a potential target for chemotherapy.

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Section: Why a Deficiency In Stem And Progenitor Cells?mentioning

confidence: 99%

The decatenation checkpoint

Damelin

Bestor

2007

Br J Cancer

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“…A comprehensive mapping of 18 histone acetylation marks in CD4 + T cells revealed that H3K9ac, H3K18ac, and H3K27ac are mainly located in regions surrounding the transcription start sites (TSS), whereas H4K8ac is elevated in promoter and transcribed regions of active genes [8,9]. Nonetheless, the correlation of intergenic H3K9ac sites with multiple promoter and enhancer marks has been used to infer that H3K9ac can denote active enhancers as well as bivalent promoters in stem cells [10,11]. Moreover, a combination of H3K4me1 and H3K27ac can serve as a readout of active enhancers [1,2,12,13].…”

Section: Introductionmentioning

confidence: 99%

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

et al. 2018

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Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation. Here, we delineate the functional mode of transcription regulators during early myogenic differentiation using genome-wide chromatin state association. We define a role of transcriptional coactivator p300, when recruited by muscle master regulator MyoD, in the establishment and regulation of myogenic loci at the onset of myoblast differentiation. In addition, we reveal an enrichment of loci-specific histone acetylation at p300 associated active or poised enhancers, particularly when enlisted by MyoD. We provide novel molecular insights into the regulation of myogenic enhancers by p300 in concert with MyoD. Our studies present a valuable aptitude for driving condition-specific chromatin state or enhancers pharmacologically to treat muscle-related diseases and for the identification of additional myogenic targets and molecular interactions for therapeutic development.Abbreviations: MRF: Muscle regulatory factor; HAT: Histone acetyltransferase; CBP: CREB-binding protein; ES: Embryonic stem; ATCC: American type culture collection; DM: Differentiation medium; DMEM: Dulbecco’s Modified Eagle Medium; GM: Growth medium; GO: Gene ontology; GREAT: Genomic regions enrichment of annotations tool; FPKM: Fragments per kilobase of transcript per million; GEO: Gene expression omnibus; MACS: Model-based analysis for ChIP-seq

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“…This promiscuity may be a result of the epigenetic environment of the ESC genome. Indeed, it has been shown that in these cells the chromatin at promoters of numerous lineage markers, including Sox1, is characterized by histone modifications that are associated both with chromatin accessibility (methylated H3K4) and transcriptional repression (trimethylated H3K27) [53,54]. It is tempting to speculate that these bivalent structures are inherently unstable and that they are dismantled at the beginning of differentiation more rapidly than repressive marks are added at the Pou5f1 locus.…”

Section: Discussionmentioning

confidence: 99%

Single Cell Analysis Reveals Concomitant Transcription of Pluripotent and Lineage Markers During the Early Steps of Differentiation of Embryonic Stem Cells

Lanctôt

2015

Stem Cells

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The differentiation of embryonic stem cells is associated with extensive changes in gene expression. It is not yet clear whether these changes are the result of binary switch-like mechanisms or that of continuous and progressive variation. Here, I have used immunostaining and single molecule RNA fluorescence in situ hybridization (FISH) to assess changes in the expression of the well-known pluripotency-associated gene Pou5f1 (also known as Oct4) and early differentiation markers Sox1 and T-brachyury in single cells during the early steps of differentiation of mouse embryonic stem cells. I found extensive overlap between the expression of Pou5f1/Sox1 or Pou5f1/T-brachyury shortly after the initiation of differentiation towards either the neuronal or the mesendodermal lineage, but no evidence of correlation between their respective expression levels. Quantitative analysis of transcriptional output at the sites of nascent transcription revealed that Pou5f1 and Sox1 were transcribed in pulses and that embryonic stem cell differentiation was accompanied by changes in pulsing frequencies. The progressive induction of Sox1 was further associated with an increase in the average size of individual transcriptional bursts. Surprisingly, single cells that actively and simultaneously transcribe both the pluripotency-and the lineage-associated genes could easily be found in the differentiating population. The results presented here show for the first time that lineage priming can occur in cells that are actively transcribing a pluripotent marker. Furthermore, they suggest that this process is associated with changes in transcriptional dynamics. STEM CELLS 2015;33:2949-2960 SIGNIFICANCE STATEMENTEmbryonic stem cells can differentiate into various cell types. The results presented here show that this process is characterized by the existence of a transient stage at which pluripotent and lineage markers appear to be expressed in an uncorrelated fashion. This lack of correlation extends to nascent transcription, as evidenced by the detection of cells that transcribe a stem cell marker alongside a lineage one. These observations highlight the plasticity of the early differentiation process, a property which could eventually be exploited to influence the fate chosen by embryonic stem cells.

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Chromatin signatures of pluripotent cell lines

Cited by 1,227 publications

References 37 publications

The decatenation checkpoint

The decatenation checkpoint

Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation

Single Cell Analysis Reveals Concomitant Transcription of Pluripotent and Lineage Markers During the Early Steps of Differentiation of Embryonic Stem Cells

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