1. Eukaryotic Gene Regulation

2. Chromatin Structure  DNA & protein  1) Nucleosomes  DNA & histones (proteins)  DNA wrapped around 8-piece histone bead

4. Chromatin Structure  2) 30-nm chromatin fiber  3) Looped domains  Fiber loops around scaffold of nonhistone proteins  4) Metaphase chromosome  Further folding & coiling to compact

5. Chromatin Structure  In interphase, compacted chromatin: heterochromatin (not transcribed – proteins can’t reach the DNA)  Non-compacted: euchromatin (is transcribed)

6. Genomic Organization  Gene Rearrangement  Loss or shuffling of genome  Change loci of genes in somatic cells  Transposons Transposons  If it “jumps” into middle of a coding sequence, it stops normal function  Itself can be activated if near active promotor

8. Genomic Organization  10% of human genome, but many are retrotransposons  Move by means of RNA intermediate & reverse transcriptase  Process like retroviruses

10. Control of Gene Expression  Cellular Differentiation  Become specialized for a function  Only fraction of genes turned on (3-5%)  Regulated at transcription by DNA- binding proteins that receive internal & external signals

11. Control of Gene Expression  Chemical modification of chromatin also regulates transcription  1)DNA methylation  Attachment of -CH 3 groups to DNA bases (cytosine) after DNA synthesis  Inactive DNA is highly methylated (removing can possibly activate genes)

12. Control of Gene Expression  Once methylated, tend to stay that way through cell divisions  The pattern is passed on – form of genomic imprinting (it permanently turns off maternal or paternal allele)

13. Control of Gene Expression  2)Histone Acetylation  Attachment of acetyl groups (-COCH 3 ) to amino acids of histones  Changes their shape – grip DNA less  Easier to transcribe that section of DNA

14. Control of Gene Expression  3) Control elements  Noncoding DNA regulating transcription  Proximal control elements – promotor

16. Control of Gene Expression  Distal control elements (farther away) – enhancers  Causes DNA to bend so transcription factors (activators) bound to enhancers can contact proteins of TIC of promotertranscription factors  Repressors bind to control elements known as silencers (much less common)

17. Control of Gene Expression  Coordination  Need to turn genes of related function on or off at same time  No operons like prokaryotes  Each gene has own promotor, so how to coordinate?  Copies of transcription factors associate with specific control elements of related genes – they activate by same signal (through signal-transduction pathways), bind, & transcribe simultaneously

18. Control of Gene Expression  4) mRNA Degredation  5) Translation initiation  Blocked by proteins that bind to 5’ end of mRNA so ribosome cannot attach

19. Control of Gene Expression 6) Protein processing & degradation  After translation  During modification or transport of protein  FYI…To destruct protein, it is marked with a protein ‘tag’ (ubiquitin); proteasomes recognize this & degrade the protein

20. Cancer  Cancer-causing genes: oncogenes  From retroviruses  Normal gene – proto-oncogene  Normal becomes cancer in three ways:  Movement of DNA within genome  Amplification of proto-oncogene  Point mutation of proto-oncogene

22. Cancer  Tumor-suppressor genes Tumor-suppressor genes  Prevent uncontrolled growth  If damaged, cancer could result  Typical jobs:  repair damaged DNA to prevent improper accumulation  Control cell anchorage (absent in cancer)

23. Cancer  Genes often involved:  1) ras – mutated in 50% of cancers  Uses signal-transduction pathway  Ras is a G protein – end result – synthesis of protein to stimulate cell cycle  Oncogene can work without growth factor due to point mutation (issues signals by itself)

25. Cancer 2) p53 gene – mutated in 30% of cancers  S-T-pathway that makes protein that inhibits cell cycle  Uses many ways to prevent cell from passing on mutations from DNA damage  Damage to gene  no inhibition  cancer