Gene regulation
Campbell and Reece, Chapter 19
TRANSPARENCY (Fig. 19.1) successive magnifications of DNA (note scales 2
to 1400 nm
A chromosome in interphase would be 5 cm in length, in mitosis, it is coiled
to 5 micro meters
Histones with high charged positive a.a.'s (lysine, arginine)
Beads on a string, double helix makes 2 wraps arould protein
It is interesting to consider:
(1) Arrangement of DNA may put places near each other that are many nucleotides
away.
(2) Anything happening along the DNA (RNA polymerase) must deal with this
structure.
TRANSPARENCY (Fig. 19.8) expands on the information after Fig. 17.7. In
addition to the "promoter" (let's call it the "proximal promoter")
just upstream of the coding sequence (that place controlling which cells
express the protein coded for), there are additional areas further upstream
(distal and proximal control elements, enhancers, etc) that control whether
the protein is expressed.
TRANSPARENCY (Fig. 19.10) There are lots of proteins that control whether
or not the gene is active (transcribed into mRNA), and these are called
transcription factors. Three types of domains bind DNA. (A domain is a portion
of a protein.) These have certain features. (The protein jargon for such
features is "motif.")
(1) Helix-turn-helix
(2) zinc finger
(3) leucine zipper
TRANSPARENCY (Fig. 19.14) (This figure will make more sense after reviewing
the Chapter 11 material and the associated lecture
about signal transduction.) Transcription factors are ultimately controlled
by signals that come up to a cell membrane receptor. For instance (right
side of the figure), a G-protein coupled receptor can affect transcription
through a transduction cascade with kinases (enzymes that phosphorylate
proteins). Growth factors (left side of the figure) cause a receptor tyrosine
kinase (itself an enzyme) to dimerize and activate (phosphorylate itself
on tyrosine residues [amino acids]). ras is an important protein in this
cascade. It binds GTP, but it is a smaller GTP-binding protein than the
GTP binding protein on the right side of the figure.
The example given pertains to how growth factors and growth inhibiting factors
might control cell division. When cell division goes haywire, you have cancer.
ras is an acronym for rat sarcoma, and a viral gene is an oncogene of a
normal protooncogene. In other words, we do not have genes that cause cancer
(oncogenes) but rather genes that, if mutated, cause cancer, but normally
these genes encode proteins like ras that subserve important and normal
functions. If this pathway activates mitosis and runs out of control, there
is too much cell division. p53 is important in that it is a transcription
factor controlling the manufacture of proteins that inhibit the cell cycle.
A block in this pathway, and the protein is missing and cells divide too
much.
TRANSPARENCY (Fig. 19.15) here is an example (colorectal cancer) where ras
is activated and p53 is inhibited.
TRANSPARENCY (Fig. 19.6) Although the title of chapter 19 is "the organization
and control of eukaryotic genomes," I have concentrated on control
(except for fig. 19.1). I finish with this figure because it relates to
a really fundamental question I brought up in the virus lecture: How can
the genome anticipate all of the antibodies that need to be made for all
microbes (considering that they keep changing). Antibody has 4 chains which
have constant and variable regions. The variable region is variable because
there is something like RNA splicing that takes place in the DNA (!) as
the B lymphocyte differentiates.
This page was last updated 7/24/02
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