Epigenetic Mechanisms for the Formation of Chromosomal Domains I

Chromosomal domains differing in their degree of condensation become apparent on polytene chromosomes as a pattern of dark bands (chromatids as >30 nm fibers) that are separated by light interbands (chromatids as ~10 nm fibers). The pattern is conserved between tissues, suggesting a constitutive chromosomal domain organisation established and maintained by chromatin boundaries. By localization, isolating and characterizing DNA sequences from band/interband units, their associated proteins and histone modifications we try to understand the process of chromosomal domain formation. Mutation of the interband specific zinc finger protein Z4 results in a dramatic loss of band/interband structure, presumably by affecting the maintenance of chromosomal boundaries. The Z4 protein is complexed with other interband proteins like the chromodomain protein Chriz and the histone kinase Jil-1. Chriz knock down results in a similar chromosomal phenotype as mutation of Z4. Loss of Jil-1 also results in structural aberrant and condensed chromosomes. In contrast, tethering Jil-1 kinase on chromatin results in local decondensation (Deng et al., 2008). Chriz-knock down affects Jil-1 binding and interband specific histone H3S10 phosphorylation. Chriz is required for Jil-1 and Z4 binding, H3S10 interphase phosphorylation and the maintenance of chromosome structure. The DNA region required for Z4/Chriz complex binding to a defined interband region was mapped on polytene chromosomes by high resolution in situ hybridization. By ChIP on chromatin of diploid cells we could show that the complex binds to the same region in these cells too, suggesting its general role in a constituting a chromatin structure that is shared between cells of different tissues.

Principal Investigators
Saumweber, Harald Prof. i.R. Dr. rer. nat. (Details) (Cytogenetics)

Duration of Project
Start date: 02/2011
End date: 02/2014

Eggert, H., Gortchakov, A, Saumweber H. (2004) Identification of the Drosophila interband-specific protein Z4 as a DNA binding zinc-finger protein determining chromosomal structure. J. Cell Sci. 117, 4253-4264.
Gortchakov, A., Eggert, H., Gan, M., Mattow, J., Zhimulev, I.F., Saumweber, H. (2005) Chriz, a chromodomain protein specific for the interbands of Drosophila melanogaster. Chromosoma 114, 54-66.
Mendjan, S, Taipale, M, Kind, J, Holz, H, Gebhard, P, Schelder, M, Vermeulen, M, Buscaino, A, Duncan, K, Mueller, J, Wilm, M, Stunnenberg, H, Saumweber, H and Akhtar, A (2006) Nucleoporins are involved in the transcriptional regulation of dosage compensation in Drosophila. Mol Cell 21, 1-13.
Mohan, M., Bartkuhn, M., Herold, M., Philippen, A., Heinl, N., Leers, J., White, R. A. H., Renkawitz-Pohl, R., Saumweber, H., Renkawitz, R. (2007) The Drosophila insulator protein dCTCF links enhancer blocking to body patterning. EMBO J 26, 4203-4214.
Bartkuhn, M., Straub, T., Herold, M., Herrmann, M., Rathke, C., Saumweber, H., Gilfillan, G.S., Becker, P.B., Renkawitz, R. (2009) Active promoters and insulators are marked by the centrosomal protein 190. EMBO J. 28(7):877-88.
Schirling, C, Seifert, F, Kesper, D, Klebes, A, Klein-Hitpass, L, Vortkamp, A, Hoffmann, D, Saumweber, H, Ehrenhofer-Murray, AE (2010) Widespread regulation of gene expression in the Drosophila genome by the histoneacetyltransferase dTip60. Chromosoma 119, 99-113
Hoffmann, A, Brünner, M, Schwendemann, A, Strödicke, M, Karberg, S, Klebes, A, Saumweber, H, Korge, G (2010) The winged helix transcription factor JUMU regulates development, nucleolus morphology and function and chromatin organization of Drosophila melanogaster. Chromosome Res. 18, 307-324.

Last updated on 2020-25-11 at 15:49