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Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response.
Béguelin W, Teater M, Meydan C, Hoehn KB, Phillip JM, Soshnev AA, Venturutti L, Rivas MA, Calvo-Fernández MT, Gutierrez J, Camarillo JM, Takata K, Tarte K, Kelleher NL, Steidl C, Mason CE, Elemento O, Allis CD, Kleinstein SH, Melnick AM
Follicular lymphomas (FLs) are slow-growing, indolent tumors containing extensive follicular dendritic cell (FDC) networks and recurrent EZH2 gain-of-function mutations. Paradoxically, FLs originate from highly proliferative germinal center (GC) B cells with proliferation strictly dependent on interactions with T fo... |
Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/Beige Adipocytes
Jin Li, Xiaohan Pan, Guihua Pan, Zijun Song, Yao He, Susu Zhang, Xueru Ye, Xiang Yang, Enjun Xie, Xinhui Wang, Xudong Mai, Xiangju Yin, Biyao Tang, Xuan Shu, Pengyu Chen, Xiaoshuang Dai, Ye Tian, Liheng Yao, Mulan Han, Guohuan Xu, Huijie Zhang, Jia Sun, H
Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi-omics data, transferrin receptor 1 (Tfr1) is identified as a candidate for regulating thermog... |
Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR
One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me... |
Wnt5a is a transcriptional target of Gli3 and Trps1 at the onset of chondrocyte hypertrophy.
Wuelling M, Schneider S, Schröther VA, Waterkamp C, Hoffmann D, Vortkamp A
During endochondral ossification, the differentiation of proliferating into hypertrophic chondrocytes is a key step determining the pace of bone formation and the future length of the skeletal elements. A variety of transcription factors are expressed at the onset of hypertrophy coordinating the expression of differ... |
Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells.
Samudyata , Amaral PP, Engström PG, Robson SC, Nielsen ML, Kouzarides T, Castelo-Branco G
Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with... |
Development and epigenetic plasticity of murine Müller glia.
Dvoriantchikova G, Seemungal RJ, Ivanov D
The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progenitors for retinal regeneration, we investigated changes in gene expres... |
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... |
The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.
Dvoriantchikova G, Seemungal RJ, Ivanov D
The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify possible mechanisms that prevent mammalian RPE from regenerating retinal... |
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 ... |
Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability.
Iglesias N, Currie MA, Jih G, Paulo JA, Siuti N, Kalocsay M, Gygi SP, Moazed D
Histone H3 lysine 9 methylation (H3K9me) mediates heterochromatic gene silencing and is important for genome stability and the regulation of gene expression. The establishment and epigenetic maintenance of heterochromatin involve the recruitment of H3K9 methyltransferases to specific sites on DNA, followed by the re... |
Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation.
Yu R, Wang X, Moazed D
Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modificati... |
Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.
Jian X, Felsenfeld G
Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin ( gene and other genes that are involved in insulin metabolism. We have ... |
Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis.
Qian P, De Kumar B, He XC, Nolte C, Gogol M, Ahn Y, Chen S, Li Z, Xu H, Perry JM, Hu D, Tao F, Zhao M, Han Y, Hall K, Peak A, Paulson A, Zhao C, Venkatraman A, Box A, Perera A, Haug JS, Parmely T, Li H, Krumlauf R, Li L
Hox genes modulate the properties of hematopoietic stem cells (HSCs) and reacquired Hox expression in progenitors contributes to leukemogenesis. Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regula... |
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... |
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Datta M, Staszewski O, Raschi E, Frosch M, Hagemeyer N, Tay TL, Blank T, Kreutzfeldt M, Merkler D, Ziegler-Waldkirch S, Matthias P, Meyer-Luehmann M, Prinz M
Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, ... |
