Max Planck Institute of Immunobiology and Epigenetics
Freiburg, Germany

The Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany, is an interdisciplinary research institute that conducts basic research in modern immunobiology and developmental biology. It was founded in 1961 as Max Planck Institute of Immunobiology and is one of 80 institutions of the Max Planck Society. The researchers of the MPI study the development of the immune system and analyse the genes and molecules which are important for its function. They also seek to establish which factors control the maturation of immune cells and how chemical changes of the DNA influence the immune defense.In 2007, the Max Planck Institute of Immunobiology added Epigenetics as a new research area. In 2010, the institute changed its name to Max Planck Institute of Immunobiology and Epigenetics.The 1984 Nobel Prize-winning biologist Georges J. F. Köhler was a director of the institute from 1984 until his death in 1995. Wikipedia.

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Padeken J.,Friedrich Miescher Institute for Biomedical Research | Heun P.,Max Planck Institute of Immunobiology and Epigenetics
Current Opinion in Cell Biology | Year: 2014

Heterochromatin was first defined by Emil Heitz in 1928 by light microscopy. In the 1950s electron microscopy studies revealed that heterochromatin preferentially localizes to the nuclear periphery and around the nucleolus. While the use of genomic approaches led to the genome wide identification of lamina-associated and nucleolus-associated chromatin domains (LADs, NADs), recent studies now shed light on the processes mediating this topology and its dynamics. The identification of different factors on all regulatory levels, such as transcription factors, histone modifications, chromatin proteins, DNA sequences and non-coding RNAs, suggests the involvement of multiple distinct tethering pathways. Positioning at these nuclear sub-compartments is often but not always associated with transcriptional silencing, underlining the importance of the pre-existing chromatin context. © 2014 Elsevier Ltd.

Conrad T.,Max Planck Institute of Immunobiology and Epigenetics | Akhtar A.,Max Planck Institute of Immunobiology and Epigenetics
Nature Reviews Genetics | Year: 2012

Dosage compensation is an epigenetic mechanism that normalizes gene expression from unequal copy numbers of sex chromosomes. Different organisms have evolved alternative molecular solutions to this task. In Drosophila melanogaster, transcription of the single male X chromosome is upregulated by twofold in a process orchestrated by the dosage compensation complex. Despite this conceptual simplicity, dosage compensation involves multiple coordinated steps to recognize and activate the entire X chromosome. We are only beginning to understand the intriguing interplay between multiple levels of local and long-range chromatin regulation required for the fine-tuned transcriptional activation of a heterogeneous gene population. This Review highlights the known facts and open questions of dosage compensation in D. melanogaster. © 2012 Macmillan Publishers Limited. All rights reserved.

Hess I.,Max Planck Institute of Immunobiology and Epigenetics | Boehm T.,Max Planck Institute of Immunobiology and Epigenetics
Immunity | Year: 2012

T cell development occurs in the thymus. The thymic microenvironment attracts hematopoietic progenitors, specifies them toward the T cell lineage, and orchestrates their differentiation and egress into the periphery. The anatomical location of the thymus and the intrauterine development of mouse embryos have so far precluded a direct visualization of the initial steps of thymopoiesis. Here, we describe transgenic zebrafish lines enabling the in vivo observation of thymopoiesis. The cell-autonomous proliferation of thymic epithelial cells, their morphological transformation into a reticular meshwork upon contact with hematopoietic cells, and the multiple migration routes of thymus-settling cells could be directly visualized. The unexpectedly dynamic thymus homing process is chemokine driven and independent of blood circulation. Thymocyte development appears to be completed in less than 4 days. Our work establishes a versatile model for the in vivo observation and manipulation of thymopoiesis. © 2012 Elsevier Inc.

Zhu Y.,Max Planck Institute of Immunobiology and Epigenetics | van Essen D.,Max Planck Institute of Immunobiology and Epigenetics | Saccani S.,Max Planck Institute of Immunobiology and Epigenetics
Molecular Cell | Year: 2012

Cell-type-specific control of gene expression is critical for the development of multicellular organisms. To investigate the mechanisms which underlie this, we have studied the regulation of the model genes Mdc and Il12b, whose stimulus-induced expression is tightly restricted to specific cells of the immune system. Surprisingly, we find that neither the promoter nor the enhancer sequences of these genes are sufficient to direct this cell-type specificity. Instead, the activities of upstream enhancers are repressed in nonexpressing cells by high levels of trimethylated H3K9 in their flanking regions. Genome-wide analysis indicates that this manner of regulation is shared by numerous enhancers of cell-type-specific genes. In dendritic cells and macrophages, the stimulus-induced demethylase Jmjd2d controls H3K9me3 levels at these regions, and is thereby required for Mdc and Il12b transcription. By experimentally assaying multiple enhancers in a variety of cell types, we show that regulation by H3K9me3 is a widely used mechanism which imparts specificity to the activities of otherwise broadly functional enhancers. © 2012 Elsevier Inc.

Arib G.,Max Planck Institute of Immunobiology and Epigenetics | Akhtar A.,Max Planck Institute of Immunobiology and Epigenetics
Current Opinion in Cell Biology | Year: 2011

Nuclear pore complexes play a central role in controlling the traffic between the nucleus and the cytoplasm. Progress during the last decade has highlighted nuclear periphery components as novel players in chromatin organization, gene regulation, and genome stability. For instance, lamins associate with repressive chromatin while nuclear pores tend to associate with active chromatin. Interestingly, nucleoporins (Nups) act not only at the nuclear periphery but also in the nucleoplasm. Here we provide an overview of the latest findings and discuss the functional importance of nucleoporin association with specific genes, their role in transcriptional memory, the coupling of transcription and mRNA export, and genome integrity. © 2011 Elsevier Ltd.

Calderon L.,Max Planck Institute of Immunobiology and Epigenetics | Boehm T.,Max Planck Institute of Immunobiology and Epigenetics
Cell | Year: 2012

Specialized niche environments specify and maintain stem and progenitor cells, but little is known about the identities and functional interactions of niche components in vivo. Here, we describe a modular system for the generation of artificial thymopoietic environments in the mouse embryo. Thymic epithelium that lacks hematopoietic function but is physiologically accessible for hematopoietic progenitor cells is functionalized by individual and combinatorial expression of four factors, the chemokines Ccl25 and Cxcl12, the cytokine Scf, and the Notch ligand DLL4. The distinct phenotypes and variable numbers of hematopoietic cells in the resulting epithelial environments reveal synergistic, context-dependent, and hierarchical interactions among effector molecules. The surprisingly simple rules determining hematopoietic properties enable the in vivo engineering of artificial environments conducive to the presence of distinct myeloid or T or B lymphoid lineage precursors; moreover, synthetic environments facilitate the procurement of physiological progenitor cell types for analytical purposes and future therapeutic applications. PaperFlick: © 2012 Elsevier Inc.

Boller S.,Max Planck Institute of Immunobiology and Epigenetics | Grosschedl R.,Max Planck Institute of Immunobiology and Epigenetics
Immunological Reviews | Year: 2014

Summary: During the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage-specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to 'prime' cis-regulatory regions for subsequent activation by the B-lineage-specific transcription factors EBF1 and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and lock cells into the B-lineage fate. In addition to the functions of EBF1 in establishing and maintaining B-cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival. © 2014 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

Iwanami N.,Max Planck Institute of Immunobiology and Epigenetics
Experimental Hematology | Year: 2014

Zebrafish is an important vertebrate model that provides the opportunity for the combination of genetic interrogation with advanced live imaging in the analysis of complex developmental and physiologic processes. Among the many advances that have been achieved using the zebrafish model, it has had a great impact on immunology. Here, I discuss recent work focusing on the genetic underpinnings of the development and function of lymphocytes in fish. Lymphocytes play critical roles in vertebrate-specific acquired immune systems of jawless and jawed fish. The unique opportunities afforded by the ability to carry out forward genetic screens and the rapidly evolving armamentarium of reverse genetics in fish usher in a new immunologic research that complements the traditional models of chicken and mouse. Recent work has greatly increased our understanding of the molecular components of the zebrafish immune system, identifying evolutionarily conserved and fish-specific functions of immune-related genes. Interestingly, some of the genes whose mutations underlie the phenotypes in immunodeficient zebrafish were also identified in immunodeficient human patients. In addition, because of the generally conserved structure and function of immune facilities, the zebrafish also provides a versatile model to examine the functional consequences of genetic variants in immune-relevant genes in the human population. Thus, I propose that genetic approaches using the zebrafish hold great potential for a better understanding of molecular mechanisms of human primary immunodeficiencies and the evolution of vertebrate immune systems. © 2014 ISEH - International Society for Experimental Hematology.

Waldmann T.,University of Konstanz | Schneider R.,Max Planck Institute of Immunobiology and Epigenetics | Schneider R.,French Institute of Health and Medical Research
Current Opinion in Cell Biology | Year: 2013

Cancer is one of the most common human diseases. It is long known that mutations in key regulator genes are hallmarks of all cancer types. Apart from these classical genetic pathways there is more and more evidence that also epigenetic alterations are crucially involved in tumourigenesis. In this review we discuss and summarise recent findings of mechanisms responsible for cancer formation apart from the classic genetic mutations. Furthermore, we show how epigenetic and genetic mechanisms could depend on each other and contribute together to cancer formation. We focus mainly on post-translational histone modifications since they are one of the major epigenetic mechanisms regulating gene expression and when they are imbalanced this can result in cancer. © 2013 Elsevier Ltd.

Boehm T.,Max Planck Institute of Immunobiology and Epigenetics
Current Biology | Year: 2012

All multicellular organisms protect themselves against pathogens using sophisticated immune defenses. Functionally interconnected humoral and cellular facilities maintain immune homeostasis in the absence of overt infection and regulate the initiation and termination of immune responses directed against pathogens. Immune responses of invertebrates, such as flies, are innate and usually stereotyped; those of vertebrates, encompassing species as diverse as jawless fish and humans, are additionally adaptive, enabling more rapid and efficient immune reactivity upon repeated encounters with a pathogen. Many of the attributes historically defining innate and adaptive immunity are in fact common to both, blurring their functional distinction and emphasizing shared ancestry and co-evolution. These findings provide indications of the evolutionary forces underlying the origin of somatic diversification of antigen receptors and contribute to our understanding of the complex phenotypes of human immune disorders. Moreover, informed by phylogenetic considerations and inspired by improved knowledge of functional networks, new avenues emerge for innovative therapeutic strategies. © 2012 Elsevier Ltd. All rights reserved.

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