Lehrstuhl für Zell- und Entwicklungsbiologie

    Chromatin architecture

    In eukaryotes DNA is packaged with proteins to form chromatin. Consequently, nuclear architecture and DNA-dependent processes rely on a regulated DNA-packaging into nucleosomal chromatin and supranucleosomal chromatin. Among the most abundant chromatin proteins associated with nucleosomal chromatin are members of the high mobility group (HMG) protein superfamily. They are considered as architectural elements of chromatin. Today it is clear that HMG-proteins belong to a network of dynamic chromatin proteins that constantly move around the chromatin fiber and thereby dynamically either promote or suppress DNA-dependent processes such as transcription, replication and DNA-repair.
    Besides the modulation of local chromatin near regulatory DNA-elements, HMG proteins affect chromatin on a more global scale including chromatin loop formation, heterochromatin structure and chromosome condensation. Deregulated expression of HMG proteins impairs gene expression, affects differentiation processes and causes several diseases. Thus, we propose that investigations on HMG-protein functions are ideal to understand local and global aspects of chromatin modulation during normal and abnormal cellular differentiation.

    Scaffolds, chromatin architecture and chromatin dynamics

    Several recent investigations have shown that nuclear architecture and function depends on dynamic behavior of proteins. High mobility of nuclear proteins guarantees their rapid and permanent availability at diverse nuclear sites, including chromatin. Whereas the basic elements of chromatin, the nucleosomes, are fairly stable basic units of DNA packaging, the nucleosomal chromatin is surrounded by a highly mobile protein crowd including HMG proteins that dynamically binds and modulates chromatin structure and function.
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    HMG-proteins and development

    During cellular differentiation and embryonic development the composition of chromatin changes and influences the expression of genes and the stability of the genome. Results emerging from studies of human disease, genetically modified mice, and cells with altered HMG expression indicate that the expression of the HMG proteins is developmentally regulated and that changes in HMG protein levels alter the cellular phenotype and may lead to developmental abnormalities and disease. For example, HMGA proteins are overexpressed in many tumours and are linked to malignancy and growth of tumor cells.
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    Scheller, K., Sekeris, C.E., Krohne, G., Hock, R., Hansen, I.A., Scheer, U. (2000) Localization of glucocorticoid hormone receptors in mitochondria of human cells. Eur. J. Cell Biol., 279: 299

    Misteli, T., Gunjan, A., Hock, R., Bustin, M., Brown, D.T. (2000) Dynamic binding of histone H1 to chromatin in living cells. Nature, 408: 877

    Lührs*, H., Hock*, R., Schauber, J., Weihrauch, M., Harrer, M., Melcher, R., Scheppach, W., Bustin, M., Menzel, T. (2002) Modulation of HMGN2 binding to chromatin by butyrate induced acetylation in human colon adenocarcinoma cells. Int. J. Cancer, 97: 567-573. (*equal contribution)

    Stöck, M., Lamatsch, D.K. , Steinlein, C., Epplen, J.T., Grosse, W.R., Hock, R., Klapperstück, T., Lampert, K.P., Scheer, U., Schmid, M., Schartl, M. (2002) A bisexually reproducing all-triploid vertebrate. Nature Gen., 30: 325-328.

    Christensen, M.O., Larsen, M.K., Barthelmes, H.U., Hock, R., Andersen, C.L., Kjeldsen, E., Knudsen, B.R., Westergaard, O., Boege, F., Mielke, C. (2002) Dynamics of human DNA topoisomerases II and II in living cells. J. Cell Biol., 157: 31-44.

    Prymakowska-Bosak*, M., Hock*, R., Catez, F., Lim, J-H., Birger, Y., Shirakawa, H., Lee, K., Bustin, M. (2002) Mitotic phosphorylation of HMGN chromosomal proteins inhibit their nuclear import and promotes interaction with 14-3-3 proteins. Mol. Cell Biol., 22: 6809-6819 (*equal contribution).

    Körner, U., Bustin, M., Scheer, U., Hock, R. (2003) Developmental role of HMGN proteins in Xenopus laevis. Mech. Dev., 120: 1177-1192.

    Harrer, M., Lührs, H., Bustin, M., Scheer, U., Hock, R. (2004) Dynamics of HMGA1 proteins in vivo. J. Cell Sci., 117: 3459-3471.

    Christensen, M.O., Krokowski, R.M., Barthelmes, H.U., Hock, R., Boege, F., Mielke, C. (2004). Distinct effects of topoisomerase I and RNA polymerase inhibitors suggest a dual mechanism of nucleolar/nucleoolasmic partitioning of topoisomerase I. J. Biol. Chem., 279: 21873-21882.

    Hock, R., Witte, F., Brocher, J., Schütz M., Scheer U. (2006) Expression of HMGA2 variants during oogenesis and early embryogenesis of Xenopus laevis. Eur. J. Cell Biol., 85: 519-528.

    Ramírez T., Stopper H, Hock R., Herrera .LA. (2007) Prevention of aneuploidy by S-adenosyl-methionine in human .cells treated with sodium arsenite. Mutat Res., 617(1-2):16-22.

    Ramírez T., Stopper H., Fischer T., Hock R., Herrera L.A. (2008) S-adenosyl-L-methionine counteracts mitotic disturbances and cytostatic effects induced by sodium arsenite in HeLa cells. Mutat Res., 637(1-2):152-60.

    Ramirez T., Brocher J., Stopper H., Hock R. (2008) Sodium arsenite modulates histone acetylation, histone deacetylase activity and HMGN protein dynamics in human cells. Chromosoma,117(2):147-57.

    Thomae A.W., Pich D., Brocher J., Spindler M.P., Berens C., Hock R., Hammerschmidt W., Schepers A. (2008) Interaction between HMGA1a and the origin recognition complex creates site-specific replication origins. Proc. Natl. Acad. Sci. USA,105(5):1692-7.

    Cherukuri S., Hock R., Ueda T., Catez F., Rochman M., Bustin M. (2008) Cell cycle-dependent binding of HMGN proteins to chromatin. Mol Biol Cell.,19(5):1816-24.

    Brocher J., Vogel B., Hock R.(2010) HMGA1 down-regulation is crucial for chromatin composition and a gene expression profile permitting myogenic differentiation. BMC Cell Biol., Aug 11:64.

    Vogel, B, Löschberger, A, Sauer, M., Hock, R (2011). Cross-linking of DNA through HMGA1 suggests as DNA scaffold. Nucleic Acids Res. 39: doi:10.1093/nar/gkr396


    Catez, F., Lim, J-H., Hock, R., Postnikov, Y. Bustin, M. (2003) HMGN dynamics and chromatin function. Biochem. Cell Biol., 81: 1-10.

    Hock, R., Furusawa, T., Ueda T, Bustin, M. (2007) HMG chromosomal proteins in development and disease. Trends Cell Biol., 17: 72-79.

    Gerlitz G., Hock R., Ueda T., Bustin M. (2009) The dynamics of HMG protein-chromatin interactions in living cells. Biochem Cell Biol., 87(1):127-137.

    Catez F., Hock R. (2010) Binding and interplay of HMG proteins on chromatin: lessons from live cell imaging. Biochim Biophys Acta., 1799 (1-2):15-27.


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