Abstracts (poster) - Wissenschaft Online

Szabolcs Sörös, Wolfgang Fischle
Molecular insights into HP1-chromatin interaction
Heterochromatin protein 1 (HP1) was initially identified as a non-histone component of
chromatin that predominantly localizes to pericentromers [1] . In vivo colocalization of HP1
with H3K9me3 in heterochromatic regions is dependent on both, the chromo-domain and
a functional chromo-shadow-domain [2] . Systematic examination of Drosophila mutants
and various in vivo experiments implicate HP1 in formation and propagation of a
heterochromatic environment defined by tight chromatin structures and transcriptional
silencing [3, 4] . However, on a molecular level, very little is known about how HP1
mediates heterochomatinization.
Here, we present a well-defined in vitro oligonucleosome system that allows precise
characterization of both, the nature of HP1 association with chromatin and the
consequences of HP1 recruitment for chromatin structure. Our data show that binding of
HP1 to recombinant oligonucleosomes is predominantly determined by the H3K9
methylation status. Very alike to the in vivo situation, the association is mediated by
both, the HP1 chromo-domain and the chromo-shadow-domain. Interestingly, binding is
enhanced under ionic conditions that lead to a condensed 30 nm-like oligonucleosome
structure. Using biochemical and biophysical approaches like dynamic light scattering,
and atomic force microscopy we examined the impact of HP1 on chromatin structure.
Our results suggest that HP1 mediates a dramatic change in conformation and
association of oligonucleosomal arrays. This effect is strongly dependent on the
methylation status of H3K9, the HP1 chromo-domain, and its chromo-shadow-domain.
Our findings manifest HP1 as a key effector in establishing higher chromatin
condensation states in heterochromatic regions.
Literature
1. James, T.C. and S.C. Elgin, Mol Cell Biol, 1986. 6: p. 3862-3872.
2. Cheutin, T., A.J. McNairn, T. Jenuwein, D.M. Gilbert, P.B. Singh, and T. Misteli,
Science, 2003. 299(5607): p. 721-5.
3. Cryderman, D.E., M.H. Cuaycong, S.C. Elgin, and L.L. Wallrath, Chromosoma, 1998.
107(5): p. 277-85.
4. Brink, M.C., Y. van der Velden, W. de Leeuw, J. Mateos-Langerak, A.S. Belmont, R.
van Driel, and P.J. Verschure, Histochem Cell Biol, 2006. 125(1-2): p. 53-61.
contact:
Szabolcs Sörös
Max Planck Institute for Biophysical Chemistry
ssoeroe@gwdg.de
Am Fassberg 11
37077 Göttingen (Germany)