Abstracts (poster) - Wissenschaft Online

Nathalie Jurisch, Bjoern Textor, Peter Angel, Marina Schorpp-Kistner
Involvement of JunB in post-translational HDAC6 regulation
and chromatin remodelling
The AP-1 transcription factor, consisting of homo- or heterodimers between the
members of the Jun and Fos protein families, is implicated in a number of biological
processes such as cellular differentiation, cell cycle progression, apoptosis and
tumorigenesis. Within the AP-1 family, JunB has an exceptional position since it has
been early demonstrated to function as a repressor on a variety of AP-1 target genes.
Moreover, studies on conventional and conditional junB knock-out mice have revealed
both positive and negative functions for JunB in influencing the control of cell
proliferation, apoptosis and differentiation. Since microarray analysis revealed that JunB
can repress many different targets genes and only activate a few ones at the same time
in the same cell, one could speculate whether JunB exerts its specific regulatory function
via chromatin remodelling.
In order to investigate the putative role of JunB in epigenetics, we first screened the
expression of histones deacetylases (HDACs) as well as the expression of some
scaffolding proteins targeting these enzymes to the DNA. JunB deficient primary and
immortalised mouse embryonic fibroblasts showed a decreased level of the histone
deacetylase HDAC6. Surprisingly, this effect was not due to transcriptional regulation by
JunB but rather due to protein instability in absence of JunB. Current studies address
first the consequences of the decreased HDAC6 expression on gene de-repression and
second the molecular mechanism responsible for HDAC6 instability in the JunB-deficient
fibroblasts.
The final goal of these studies will be to determine the genetic network driven by JunB
and HDAC6 that controls cell identity and function in normal development but also in
disease such as inflammation-associated disorders and cancer.
contact:
Nathalie Jurisch
German Cancer Research Centre
n.jurisch@dkfz.de
Im Neuenheimer Feld 280
69120 Heidelberg (Germany)