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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