Publications
164 results found
Piccolo FM, Bagci H, Brown KE, et al., 2013, Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion (vol 49, pg 1023, 2013), MOLECULAR CELL, Vol: 49, Pages: 1176-1176, ISSN: 1097-2765
Merkenschlager M, Odom DT, 2013, CTCF and Cohesin: Linking Gene Regulatory Elements with Their Targets, CELL, Vol: 152, Pages: 1285-1297, ISSN: 0092-8674
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- Citations: 264
Ferreiros-Vidal I, Carroll T, Taylor B, et al., 2013, Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation, BLOOD, Vol: 121, Pages: 1769-1782, ISSN: 0006-4971
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- Citations: 82
Tsubouchi T, Soza-Ried J, Brown K, et al., 2013, DNA Synthesis Is Required for Reprogramming Mediated by Stem Cell Fusion, CELL, Vol: 152, Pages: 873-883, ISSN: 0092-8674
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- Citations: 60
Peng C, Li N, Ng Y-K, et al., 2012, A Unilateral Negative Feedback Loop Between <i>miR</i>-<i>200</i> microRNAs and Sox2/E2F3 Controls Neural Progenitor Cell-Cycle Exit and Differentiation, JOURNAL OF NEUROSCIENCE, Vol: 32, Pages: 13292-13308, ISSN: 0270-6474
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- Citations: 77
Merkenschlager M, Seitan V, Tachibana K, et al., 2012, Cohesin regulates T cell receptor rearrangement and thymocyte differentiation, 1st Biennial Symposium on Regulatory T Cells and T Helper Cells, Publisher: WILEY-BLACKWELL, Pages: 3-3, ISSN: 0019-2805
Seitan VC, Merkenschlager M, 2012, Cohesin and chromatin organisation, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 22, Pages: 93-100, ISSN: 0959-437X
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- Citations: 33
Seitan VC, Krangel MS, Merkenschlager M, 2012, Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement, TRENDS IN IMMUNOLOGY, Vol: 33, Pages: 153-159, ISSN: 1471-4906
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- Citations: 24
Clemente-Blanco A, Sen N, Mayan-Santos M, et al., 2011, Cdc14 phosphatase promotes segregation of telomeres through repression of RNA polymerase II transcription, Nature Cell Biology, Vol: 13, Pages: 1450-U163, ISSN: 1465-7392
Kinases and phosphatases regulate messenger RNA synthesis through post-translational modification of the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (ref. 1). In yeast, the phosphatase Cdc14 is required for mitotic exit2,3 and for segregation of repetitive regions4. Cdc14 is also a subunit of the silencing complex RENT (refs 5, 6), but no roles in transcriptional repression have been described. Here we report that inactivation of Cdc14 causes silencing defects at the intergenic spacer sequences of ribosomal genes during interphase and at Y′ repeats in subtelomeric regions during mitosis. We show that the role of Cdc14 in silencing is independent of the RENT deacetylase subunit Sir2. Instead, Cdc14 acts directly on RNA polymerase II by targeting CTD phosphorylation at Ser 2 and Ser 5. We also find that the role of Cdc14 as a CTD phosphatase is conserved in humans. Finally, telomere segregation defects in cdc14 mutants4 correlate with the presence of subtelomeric Y′ elements and can be rescued by transcriptional inhibition of RNA polymerase II.
Seitan V, Tachibana K, Hao B, et al., 2011, How cohesin regulates gene expression and differentiation in non-dividing mammalian cells, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 21-21, ISSN: 0019-2805
Seitan VC, Hao B, Tachibana-Konwalski K, et al., 2011, A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation, Nature, Vol: 476, Pages: 467-U126, ISSN: 0028-0836
Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis1. There is growing evidence that cohesin also forms long-range chromosomal cis-interactions2,3,4 and may regulate gene expression2,3,4,5,6,7,8,9,10 in association with CTCF8,9, mediator4 or tissue-specific transcription factors10. Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions7, but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion—as exemplified in Drosophila11,12,13—has not been demonstrated in vertebrate systems. To address this, here we deleted the cohesin locus Rad21 in mouse thymocytes at a time in development when these cells stop cycling and rearrange their T-cell receptor (TCR) α locus (Tcra). Rad21-deficient thymocytes had a normal lifespan and retained the ability to differentiate, albeit with reduced efficiency. Loss of Rad21 led to defective chromatin architecture at the Tcra locus, where cohesion-binding sites flank the TEA promoter and the Eα enhancer, and demarcate Tcra from interspersed Tcrd elements and neighbouring housekeeping genes. Cohesin was required for long-range promoter–enhancer interactions, Tcra transcription, H3K4me3 histone modifications that recruit the recombination machinery14,15 and Tcra rearrangement. Provision of pre-rearranged TCR transgenes largely rescued thymocyte differentiation, demonstrating that among thousands of potential target genes across the genome4,8,9,10, defective Tcra rearrangement was limiting for the differentiation of cohesin-deficient thymocytes. These findings firmly establish a cell-division-independent role for cohesin in Tcra locus rearrangement and provide a comprehensive account of the mechanisms by which cohesin enables cellular differentiation in a well-characterized mammali
Piccolo FM, Pereira CF, Cantone I, et al., 2011, Using heterokaryons to understand pluripotency and reprogramming, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 366, Pages: 2260-2265, ISSN: 0962-8436
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- Citations: 23
Soza-Reid J, Tsubouchi T, Brown K, et al., 2011, Pluripotent stem cells and epigenetic reprogramming, 36th FEBS Congress of the Biochemistry for Tomorrows Medicine, Publisher: WILEY-BLACKWELL, Pages: 8-8, ISSN: 1742-464X
Mazzarella L, Jorgensen HF, Soza-Ried J, et al., 2011, Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression, BLOOD, Vol: 117, Pages: 83-87, ISSN: 0006-4971
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- Citations: 13
Merkenschlager M, 2010, Ikaros in immune receptor signaling, lymphocyte differentiation, and function, FEBS LETTERS, Vol: 584, Pages: 4910-4914, ISSN: 0014-5793
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- Citations: 51
Konopka W, Kiryk A, Novak M, et al., 2010, MicroRNA Loss Enhances Learning and Memory in Mice, JOURNAL OF NEUROSCIENCE, Vol: 30, Pages: 14835-14842, ISSN: 0270-6474
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- Citations: 232
Merkenschlager M, 2010, Cohesin: a global player in chromosome biology with local ties to gene regulation, CURRENT OPINION IN GENETICS & DEVELOPMENT, Vol: 20, Pages: 555-561, ISSN: 0959-437X
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- Citations: 36
Spruce T, Pernaute B, Di-Gregorio A, et al., 2010, An Early Developmental Role for miRNAs in the Maintenance of Extraembryonic Stem Cells in the Mouse Embryo, DEVELOPMENTAL CELL, Vol: 19, Pages: 207-219, ISSN: 1534-5807
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- Citations: 67
Zhao J, Lee M-C, Momin A, et al., 2010, Small RNAs Control Sodium Channel Expression, Nociceptor Excitability, and Pain Thresholds, JOURNAL OF NEUROSCIENCE, Vol: 30, Pages: 10860-10871, ISSN: 0270-6474
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- Citations: 133
Guo S, Lu J, Schlanger R, et al., 2010, MicroRNA miR-125a controls hematopoietic stem cell number, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 14229-14234, ISSN: 0027-8424
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- Citations: 266
Merkenschlager M, von Boehmer H, 2010, PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo factors, Journal of Experimental Medicine, Vol: 207, Pages: 1347-1350, ISSN: 0022-1007
Expression of the regulatory T (T reg) cell–associated transcription factor Foxp3 can be induced by signals from the T cell receptor (TCR), interleukin-2 (IL-2), and transforming growth factor (TGF)-β. These signals are integrated by a network involving phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB; here referred to as Akt), and the mammalian target of rapamycin (mTOR). New studies show that the Foxo proteins Foxo1 and Foxo3a, which are inactivated by Akt, drive Foxp3 expression. These studies therefore explain the negative regulation of Foxp3 by PI3K signaling, and add Foxo proteins to the growing list of nuclear factors capable of modulating Foxp3 expression.
Fisher AG, Merkenschlager M, 2010, Fresh powder on Waddington's slopes, EMBO REPORTS, Vol: 11, Pages: 490-492, ISSN: 1469-221X
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- Citations: 3
Landeira D, Sauer S, Poot R, et al., 2010, Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators, NATURE CELL BIOLOGY, Vol: 12, Pages: 618-U214, ISSN: 1465-7392
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- Citations: 236
Raaijmakers MHGP, Mukherjee S, Guo S, et al., 2010, Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia, Nature, Vol: 464, ISSN: 0028-0836
Mesenchymal cell populations contribute to microenvironments regulating stem cells and thegrowth of malignant cells. Osteolineage cells participate in the hematopoietic stem cell niche.Here, we report that deletion of the miRNA processing endonuclease Dicer1 selectively inmesenchymal osteoprogenitors induces markedly disordered hematopoiesis. Hematopoieticchanges affected multiple lineages recapitulating key features of human myelodysplasticsyndrome (MDS) including the development of acute myelogenous leukemia. These changes weremicroenvironment dependent and induced by specific cells in the osteolineage. Dicer1−/−osteoprogenitors expressed reduced levels of Sbds, the gene mutated in the human bone marrowfailure and leukemia predisposition Shwachman-Bodian-Diamond Syndrome. Deletion of Sbds inosteoprogenitors largely phenocopied Dicer1 deletion. These data demonstrate that differentiationstage-specific perturbations in osteolineage cells can induce complex hematological disorders andindicate the central role individual cellular elements of ‘estroma’ can play in tissue homeostasis.They reveal that primary changes in the hematopoietic microenvironment can initiate secondaryneoplastic disease.
Pereira CF, Piccolo FM, Tsubouchi T, et al., 2010, ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency, Cell stem cell, Vol: 6, Pages: 547-556
Stem Cell, 6 (2010) 547-556. doi:10.1016/j.stem.2010.04.013
Santos J, Pereira CF, Di-Gregorio A, et al., 2010, Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo, Epigenetics & Chromatin, Vol: 3, ISSN: 1756-8935
BackgroundDuring early mouse development, two extra-embryonic lineages form alongside the future embryo: the trophectoderm (TE) and the primitive endoderm (PrE). Epigenetic changes known to take place during these early stages include changes in DNA methylation and modified histones, as well as dynamic changes in gene expression.ResultsIn order to understand the role and extent of chromatin-based changes for lineage commitment within the embryo, we examined the epigenetic profiles of mouse embryonic stem (ES), trophectoderm stem (TS) and extra-embryonic endoderm (XEN) stem cell lines that were derived from the inner cell mass (ICM), TE and PrE, respectively. As an initial indicator of the chromatin state, we assessed the replication timing of a cohort of genes in each cell type, based on data that expressed genes and acetylated chromatin domains, generally, replicate early in S-phase, whereas some silent genes, hypoacetylated or condensed chromatin tend to replicate later. We found that many lineage-specific genes replicate early in ES, TS and XEN cells, which was consistent with a broadly 'accessible' chromatin that was reported previously for multiple ES cell lines. Close inspection of these profiles revealed differences between ES, TS and XEN cells that were consistent with their differing lineage affiliations and developmental potential. A comparative analysis of modified histones at the promoters of individual genes showed that in TS and ES cells many lineage-specific regulator genes are co-marked with modifications associated with active (H4ac, H3K4me2, H3K9ac) and repressive (H3K27me3) chromatin. However, in XEN cells several of these genes were marked solely by repressive modifications (such as H3K27me3, H4K20me3). Consistent with TS and XEN having a restricted developmental potential, we show that these cells selectively reprogramme somatic cells to induce the de novo expression of genes associated with extraembryonic differentiation.ConclusionsThese data p
Kim G-J, Georg I, Scherthan H, et al., 2010, <i>Dicer</i> is required for Sertoli cell function and survival, INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, Vol: 54, Pages: 867-875, ISSN: 0214-6282
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- Citations: 63
Bruno L, Mazzarella L, Hoogenkamp M, et al., 2009, Runx proteins regulate Foxp3 expression, Journal of Experimental Medicine, Vol: 206, Pages: 2329-2337, ISSN: 0022-1007
Runx proteins are essential for hematopoiesis and play an important role in T cell development by regulating key target genes, such as CD4 and CD8 as well as lymphokine genes, during the specialization of naive CD4 T cells into distinct T helper subsets. In regulatory T (T reg) cells, the signature transcription factor Foxp3 interacts with and modulates the function of several other DNA binding proteins, including Runx family members, at the protein level. We show that Runx proteins also regulate the initiation and the maintenance of Foxp3 gene expression in CD4 T cells. Full-length Runx promoted the de novo expression of Foxp3 during inducible T reg cell differentiation, whereas the isolated dominant-negative Runt DNA binding domain antagonized de novo Foxp3 expression. Foxp3 expression in natural T reg cells remained dependent on Runx proteins and correlated with the binding of Runx/core-binding factor β to regulatory elements within the Foxp3 locus. Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes.
Fedeli M, Napolitano A, Wong MPM, et al., 2009, Dicer-Dependent MicroRNA Pathway Controls Invariant NKT Cell Development, JOURNAL OF IMMUNOLOGY, Vol: 183, Pages: 2506-2512, ISSN: 0022-1767
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- Citations: 75
Spruce T, Pernaute B, di Gregorio A, et al., 2009, Essential roles for microRNAs in stem cell maintenance in the early mouse embryo, 16th Annual Conference of the International-Society-of-Development-Biologists, Publisher: ELSEVIER SCIENCE BV, Pages: S49-S49, ISSN: 0925-4773
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