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Assistant Professor Jorg Bungert earned his Ph.D. in 1992 at
the Philipps University in Marburg (Germany) for his work with Dr. K. H.
Seifart on the isolation and characterization of erythroid-specific RNA
polymerase II transcription complexes. He was a Postdoctoral Fellow in
the laboratory of Dr. J. D. Engel at Northwestern University where he investigated
the regulation of the human beta-globin gene locus using yeast artificial
chromosomes (YACs) and transgenic mice. He joined the Department in 1998.
Research Interests:
The human beta-globin locus control region (LCR) is a powerful DNA regulatory
element composed of five DNaseI hypersensitive sites (HS1 to HS5) and located
from 8 to 22 Kbp upstream of the human epsilon-globin gene. The LCR induces
chromatin opening over the whole beta-globin gene locus and is also required
for high level globin gene expression throughout erythroid development.
Our previous work suggest that the individual HS elements interact to generate
a higher order structure, referred to as the LCR holocomplex, and that
this complex communicates in a stage specific manner with individual globin
genes. We are interested in the question of how the HS sites synergize
to generate a fully active LCR. To address this question, we use both genetic
as well as biochemical assays. In order to identify DNA elements critically
involved in LCR function, we are analyzing the effect of specific LCR mutations
on chromatin structure and expression of the globin genes in human beta-globin
YAC transgenic mice. Second, in order to examine mutual interactions between
LCR HS elements, we generate HS sites in vitro, using chromatin assembly
in combination with erythroid-specific protein extracts, and analyze these
macromolecular protein/DNA complexes with a variety of biochemical and
biophysical techniques.
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