of the Max - MDC

Structure of the Group
Group Leader
Dr. M. Cristina Cardoso
Scientists
Dr. Volker Buschmann*
Dr. Sabine M. Görisch*
Sebastian Haase*
Dr. Jeffrey H. Stear*
Graduate Students
Noopur Agarwal
Annette Becker*
Corella Casas Delucchi*
K. Laurence Jost*
Robert M. Martin
Gisela Tünnemann
Technical Assistants
Petra Domaing
Marion Fillies* (part-time)
Maria Hofstätter*
Danny Nowak (part-time)
Secretariat
Annette Schledz*
* part of the period reported
to sites of DNA methylation and then recruit other chromatin
modifiers such as histone deacetylase complexes.
MeCP2, the founding member of the MBD family, is mutated
in most Rett syndrome patients, which is the second most
common neurological disorder after Down syndrome.
We have found that MBDs induce large-scale heterochromatin
reorganization during terminal differentiation. Based
on this finding, we are currently dissecting the mechanisms
responsible for this chromatin reorganization by a combination
of in vitro and in vivo approaches including biochemical
and photodynamic assays. Furthermore, we are testing the
molecular composition and role of these heterochromatin
compartments in genome expression/silencing during differentiation
and in disease.
This should help to elucidate the role of genome topology in
cellular differentiation, and provide new ways to manipulate
the phenotypic plasticity of cells for application in cell
replacement therapies in regenerative medicine.
Accessing the (epi)genome
(V. Buschmann, S. M. Görisch, R. M. Martin,
G. Tünnemann)
Nuclear DNA is organized together with structural proteins
into dynamic higher order chromatin structures, which
reflect and control gene expression during the cell division
cycle and cellular differentiation. Chromatin can be subdivided
into eu- and heterochromatin, depending on its condensation
state, transcriptional activity and the modification
of associated chromatin organizing proteins,. Whereas
euchromatin is generally assumed to be actively transcribed
and less condensed, heterochromatin condensation is
thought to be similar to mitotic chromosomes in which DNA
metabolism, (e.g. transcription and replication) has
stopped. It is unclear whether and how changes in the
chromatin compaction state affect the mobility of chromatin
organizing proteins and the access of proteins to chromatin.
To address these questions, we are using a combination of
live-cell chromatin labels and high-speed single molecule
tracing microscopy as well as photodynamic assays in living
mammalian cells. In parallel, we are evaluating and exploiting
novel non-invasive methods to introduce molecules into
cells directly via peptide transducing domains that can cross
cellular membranes. These techniques will allow us to compare
the accessibility and mobility of proteins in different
subnuclear compartments. In particular, we are interested
in elucidating the physico-chemical principles regulating
genome accessibility and, thus, controlling nuclear
metabolism.
Selected Publications
Brero, A, Easwaran, H P, Nowak, D, Grunewald, I, Cremer, T,
Leonhardt, H and Cardoso, M C. (2005). Methyl CpG binding
proteins induce large-scale chromatin reorganization during
terminal differentiation. J. Cell Biol., 169: 733-743.
Sporbert, A, Domaing, P, Leonhardt, H and Cardoso, MC.
(2005). PCNA acts as a stationary loading platform for
transiently interacting Okazaki fragment proteins. NAR,
33: 3521-3528.
Rothbauer, U, Zolghadr, K, Tillib, S, Nowak, D, Schermelleh, L,
Gahl, A, Backmann, N, Conrath, K, Muyldermans, S, Cardoso, M
C, and Leonhardt, H. (2006). Targeting and tracing of antigens
in living cells with fluorescent nanobodies. Nature Methods
3: 887-889.
Agarwal, N, Hardt, T, Brero, A, Nowak, D, Rothbauer, U, Becker,
A, Leonhardt, H, Cardoso, M C. (2007). MeCP2 interacts with
HP1 and modulates its heterochromatin association during
myogenic differentiation. NAR 35: 5402-5408.
Martin, RM, Görisch, SM, Leonhardt, H and Cardoso, MC. (2007)
An unexpected link between energy metabolism, calcium,
chromatin condensation and cell cycle. Cell Cycle In Press.
Cardiovascular and Metabolic Disease Research 45