1. Chapter 18.2-5 Eukaryotic Genomes

2. 18.2 Gene expression
Cell differentiation - process that specializes the form and function of each type of cell in multi-cellular organisms
*humans have over 200 different types of cells
* about 20% of genes are expressed in humans
*1.5% of DNA codes for proteins
- smaller fraction codes for rRNA and tRNA
– rest is noncoding, may also transcribe into RNA with unknown functions

3. Chromatin Structure
Chromatin – the DNA-protein complex found in eukaryotes
-many structrural changes occur during cell cycle
-Interphase- diffuse mass in the nucleus
-G2 – coils up and condenses
-Mitosis – apparent chromosome structure or sister chromatids

4. Histones
Histones – proteins responsible for first level of DNA packing in chromatin
- most histones are similar in eukaryotes as well as prokaryotes
-gives evolutionary significance to the role histones play in organizing DNA in cells
Nucleosomes – basic unit of DNA packing
-consists of DNA wound around protein core and containing two molecules of 4 types of histones
-changes to the shapes and positions of nucleosome can allow RNA polymerases to move along DNA

5. Histone Modifications
Mounting evidence indicates that chemical modifications to histones plays a direct role in regulation of gene transcription
Histone acetylation – attaching an acetyl group (COCH3) will loosen the condensed chromatin and in turn initiate transcription and recruit factors for the machinery
Deacetylation – most likely inhibits transcription

6. DNA Methylation
Attachment of methyl groups (CH3) to tail of DNA is thought to be essential for long term inactivation of certain genes
*Genomic imprinting - patterns of methylation passes from parent to offspring keeping record of what occurred during development
-permanently regulates expression of either maternal or paternal allele of certain genes

7. Enhancers for Transcription

8. Regulation of Transcription
Control elements – segments of noncoding DNA that serve as binding sites for proteins (transcription factors) in eukaryotes
2 categories of Transcription factors
1. general factors – essential for all protein coding genes
2. specific factors – high levels of transcription of particular genes at appropriate time and place
-will increase or decrease rate of gene expression
Ex: proximal – close to promotor
distal (enhancers) – far from promotor or even in intron

9. Critical Gene Expression
Transcription is the most critical stage in controlling gene expression
- enhancers matching control elements to each specific gene can activate machinery
mRNA degradation and translation can also be checkpoints
Proteasomes- giant protein complex that recognizes ubiquitin tagged proteins and cuts into small peptides initiating the degradation process

10. Degradation by Proteasomes

11. 18.3 Noncoding DNA
Coding for proteins and RNA products is only a tiny portion of the genome
Bulk of genomes is mostly noncoding or “junk DNA”
*Must have important role to persist for hundreds of generations
Ex: human genome has 500 to more base pairs in DNA compared to bacteria, but only 5 to 15 times more genes

12. Noncoding mRNA
Its now believed that 75% of the genome is transcribed at some of a given cell
mRNA may be non protein coding but still serve a purpose in controlling gene expression
2 examples:
1. Micro RNAs(miRNA) - bind to complementary RNA, degrades or blocks translation
2. Small interfering RNA(siRNA) - similar to miRNA, but can bind and turn off gene expression (like methylation)

13. 18.4 Embryonic Development
Morphogenesis – the development of the form of an organism and its structures - differential gene expression results from the genes being regulated differently in each cell type -materials placed in the egg by the mother determine the sequential program of regulation

14. Gene Expression Control
Important source in determining the differentiated fate comes the egg’s cytoplasm
cytoplasmic determinants – maternal substances in the egg that influence course of early development
- combinations of cytoplasmic determinants regulate expression of cell’s genes
Another source is the environment around the cell
- induction – process where signals from neighboring cells and binding of growth factors cause changes in target cells

15. Gene Expression Control
Determination – point at which an embryonic cell is irreversibly committed to becoming a particular cell type
- differentiation a cell attains its determined fate
- expression of tissue specific proteins determine the outcome of determination
- presence of mRNA in proteins marks fate
Pattern formation – process in which cytoplasmic determinants and induction signals contribute the spatial organization of tissues and organs

16. 18.5 Cancer
Growth factors, their receptors, and signal pathway molecules regulate genes that control cell growth and division
-any mutation to these genes in somatic cells can lead to cancer
-cancer causing mutations can be spontaneous or caused by environmental influences such as X-rays, chemical carcinogens, and certain viruses

17. Genes linked to Cancer
Proto-oncogens- normal cellular genes that code for proteins to stimulate growth and division
Oncogenes- cancer causing genes
How does the normal proto-oncogene become an oncogene?

18. Proto into oncogene
3 mechanisms: (common link is abnormal stimulation of cell cycle and path to malignancy)
1. Movement of DNA within the genome
2. amplification of proto-oncogene
3. point mutation in control element

19. Tumor suppression
Tumor suppressor genes – products found within the cell that inhibit cell division to prevent uncontrolled cell growth
-any mutation can reverse this activity and lead to onset of cancer

20. Interference with Signaling Pathways

21. P53 Gene P53 gene- “guardian angel of genome”
-activated by DNA damage can prevent passing of mutations 3 ways:
1. can function as an activator to signal genes to halt cell cycle and allow repair
2. can directly turn on genes involved in DNA repair
3. can cause apoptosis or cell death to genes that are irreparable

22. Multistep Progression
Usually more than one somatic mutation is needed for a cell to become full fledged cancer
Accumulations of mutations with throughout life means longer life increased likelihood of cancer
Steps:
1. appearance of a polyp (benign)
2. tumor grows and becomes malignant
3. accumulations of mutations that converts proto-oncogenes to oncogenes
4. Knock out or mutation of tumor suppressor genes

23. Multistep Progression
What percentage of cancers develop from viruses? Is inheritance a link to predisposition of cancer?