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Delineating the early transcriptional specification of the mammalian trachea and esophagus.
Kuwahara A, Lewis AE, Coombes C, Leung FS, Percharde M, Bush JO
The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By comb...
Combinatorial action of NF-Y and TALE at embryonic enhancers defines distinct gene expression programs during zygotic genome activation in zebrafish.
Stanney W, Ladam F, Donaldson IJ, Parsons TJ, Maehr R, Bobola N, Sagerström CG
Animal embryogenesis is initiated by maternal factors, but zygotic genome activation (ZGA) shifts regulatory control to the embryo during blastula stages. ZGA is thought to be mediated by maternally provided transcription factors (TFs), but few such TFs have been identified in vertebrates. Here we report that NF-Y a...
Whsc1 links pluripotency exit with mesendoderm specification.
Tian TV, Di Stefano B, Stik G, Vila-Casadesús M, Sardina JL, Vidal E, Dasti A, Segura-Morales C, De Andrés-Aguayo L, Gómez A, Goldmann J, Jaenisch R, Graf T
How pluripotent stem cells differentiate into the main germ layers is a key question of developmental biology. Here, we show that the chromatin-related factor Whsc1 (also known as Nsd2 and MMSET) has a dual role in pluripotency exit and germ layer specification of embryonic stem cells. On induction of differentiatio...
Spatial confinement downsizes the inflammatory response of macrophages.
Jain N, Vogel V
Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micropatterning, microporous substrates or cell crowding, suppresses late ...
SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human breast cancer
Khaldoun Rifaï et al.
Breast cancer is the most frequently diagnosed malignancy in women worldwide. It is well established that the complexity of carcinogenesis involves profound epigenetic deregulations that contribute to the tumorigenesis process. Deregulated H3 and H4 acetylated histone marks are amongst those alterations. Sirtuin-1 (...
Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.
Baghdadi MB, Castel D, Machado L, Fukada SI, Birk DE, Relaix F, Tajbakhsh S, Mourikis P
The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix. Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells, the co...
A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.
Daures M, Idrissou M, Judes G, Rifaï K, Penault-Llorca F, Bignon YJ, Guy L, Bernard-Gallon D
Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown to be deregulated in prostate cancer, and evidence shows H3K27me3 enri...
Contrasting epigenetic states of heterochromatin in the different types of mouse pluripotent stem cells.
Tosolini M, Brochard V, Adenot P, Chebrout M, Grillo G, Navia V, Beaujean N, Francastel C, Bonnet-Garnier A, Jouneau A
Mouse embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) represent naive and primed pluripotency states, respectively, and are maintained in vitro by specific signalling pathways. Furthermore, ESCs cultured in serum-free medium with two kinase inhibitors (2i-ESCs) are thought to be the ground naïve pl...
Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a
Ching S.T. et al.
Genital malformations are among the most common human birth defects, and both genetic and environmental factors can contribute to these malformations. Development of the external genitalia in mammals relies on complex signaling networks, and disruption of these signaling pathways can lead to genital defects. Islet-1...
In Situ Fixation Redefines Quiescence and Early Activation of Skeletal Muscle Stem Cells
Machado L. et al.
State of the art techniques have been developed to isolate and analyze cells from various tissues, aiming to capture their in vivo state. However, the majority of cell isolation protocols involve lengthy mechanical and enzymatic dissociation steps followed by flow cytometry, exposing cells to stres...
The RPMI-1640 vitamin mixture promotes bovine blastocyst development in vitro and downregulates gene expression of TXNIP with epigenetic modification of associated histones
Ikeda S.et al.
Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF)...
Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression
Ngollo M. et al.
H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression.
We investigated genome-wide H3K27me3 histone methylation profile using chromatin immunoprecipitation (ChIP) and 2X400K p...
Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice
Idoia García-Ramírez, Saber Tadros, Inés González-Herrero, Alberto Martín-Lorenzo, Guillermo Rodríguez-Hernández, Dalia Moore, Lucía Ruiz-Roca, Oscar Blanco, Diego Alonso-López, Javier De Las Rivas, Keenan Hartert, Romain Duval, David Klinkebiel, Martin B
CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can cooperate with Bcl2 over-expression to promote B-cell lymphoma. Through tra...
Aorta macrophage inflammatory and epigenetic changes in a murine model of obstructive sleep apnea: Potential role of CD36.
Cortese R. et al.
Obstructive sleep apnea (OSA) affects 8-10% of the population, is characterized by chronic intermittent hypoxia (CIH), and causally associates with cardiovascular morbidities. In CIH-exposed mice, closely mimicking the chronicity of human OSA, increased accumulation and proliferation of pro-inflammatory metabolic M1...
Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis
Shimizu T et al.
Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic cells contribute synergistically to the development of MPN. The MPN phenotype induced by JAK2-V6...
Methionine-dependent histone methylation at developmentally important gene loci in mouse preimplantation embryos
Kudo M, Ikeda S, Sugimoto M, Kume S
The involvement of specific nutrients in epigenetic gene regulation is a possible mechanism underlying nutrition-directed phenotypic alteration. However, the involvement of nutrients in gene-specific epigenetic regulation remains poorly understood. Methionine has been received attention as a possible nutrient involv...