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• Control of Gene

Expression
Chip array analysis

tumors

1800 genes
Red- up
Black- same
Green down
Blue is different
Gene expression is regulated at many levels
How was this worked out ?

Bacteria
RNA polymerase + a factor
Eucaryotes
Didn’t know what a promotor was , Ad major late .
Extract that works ,looking for sigma factor
Manley
Roeder.
Reinberg, Tijan

DNA
A Positive Regulatory Element Maps
Between -115 and -153

-1004 Luc

-890 Luc
-681 Luc

-428 Luc

-248 Luc

-228 Luc

-195 Luc

-153 Luc
-115 Luc
0 10 20 30 40 50 60

Fold Activation
How do gene regulatory proteins work?
What is seen on the DNA ?
Sequence specific but do not unwind

Most proteins bind to the


major groove
What are structural characteristics of the
gene regulatory proteins ?

The simplest and most typical is the

helix-turn-helix
The homeodomain is a helix-turn -helix protein
The zinc finger - reiterations can strengthen interaction
The glucocorticoid receptor has two zinc fingers
A specific regulatory factor for each gene ? NO!!
Heterodimers-leucine zippers
The Heliz-loop-helix motif mediates Dimerization and DNA binding

Another solution to number problem


Complex expression patterns are a result of the concerted action
of discrete simpler elements
Regulation of transcription by covalent modification of
DNA

Methylation

CpG

May explain heritable patterns of gene expression


Regulation of gene expression by RNA itself

Do transcription factors contain RNA ?

Regulation of processing and expression by RNA