Lecture #8 Date _________

Chapter 19~ The Organization and Control of Eukaryotic Genomes

Chromatin

Def: complex of DNA and proteins DNA Packing •histone protein (+ charged

amino acids ~ phosphates of DNA are - charged)

Nucleosome •”beads on a string”; basic unit of DNA packing

Heterochromatin •highly condensed interphase DNA (can not be transcribed)

Euchromatin •less compacted interphase DNA (can be transcribed)

DNA Packing

Stages of gene regulation/expression

only express a small number of genes

cellular differentiation chromatic modification transcription RNA processing RNA transport translation protein processing and

degradation

Chromatin Modification

Genes with highly packed heterochromatin usually not expressed

Histone acetylation – loosens heterochromatic structure enhancing transcription

Addition of methyl groups to DNA bases can reduce transcription

Typical Eukaryotic Gene

most eukaryotic genes have multiple control elements – segments of noncoding DNA that help regulate transcription

proximal control elements – close to the promoter distal control elements – usually called enhancers, located further

upstream than proximal control elements

Eukaryotic gene regulation an activator – a protein that

binds to an enhancer and stimulates gene transcription

there are no operons in eukaryotic organisms, but genes in a group will have the same regulatory sequences to coordinate expression, example heat shock response and steroid hormone action

flash movie

RNA Processing

different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns

flash movie

mRNA Degradation

longevity of mRNA affects how much protein synthesis it directs

some can last for minutes, some for weeks

degradation could begin with the removal of the 5’ cap or the poly A tail

Control of Translation

can repress initiation of translation repressor proteins that bind to specific

sequences or structures within the leader region at the 5’ end preventing ribosome attachment (local control)

inactivate necessary transcription factors (global control)

Protein Processing many polypeptides need

modified before they can properly function – addition of sugars, lipids, additional amino acids; cleaving chain into two or more pieces

can alter the targeting of a protein – if the protein cannot reach the target site, it cannot function

select a protein for degradation – attach ubiquitin, large proteasomes recognize ubiquitin and degrade the protein (could lead to cancer if cell cycle proteins become impervious to proteasomes)

Protein Degradation

select a protein for degradation – attach ubiquitin, large proteasomes recognize ubiquitin and degrade the protein (could lead to cancer if cell cycle proteins become impervious to proteasomes)

Molecular Biology of Cancer Oncogene •cancer-

causing genes Proto-oncogene

•normal cellular genes How?

1-movement of DNA; chromosome fragments that have rejoined incorrectly 2-amplification; increases the number of copies of proto-oncogenes

3-proto-oncogene point mutation; protein product more active or more resistant to degradation

Tumor-suppressor genes •changes in genes that prevent uncontrolled cell growth (cancer growth stimulated by the absence of suppression)

The Human Genome

98.5% of the human genome does not code for protein, rRNA, or tRNA

transposable elements (jumping genes) – transposons (DNA intermediate) and retrotransposons (RNA intermediate)

simple sequence DNA – repeating units found in centromeres and telomeres

Alu elements – 300 nucleotides long, do not code for protein but many are transcribed into protein, function unknown