Eukaryotic Gene Regulation. Chromatin Structure DNA & protein 1) Nucleosomes DNA & histones...
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Transcript of Eukaryotic Gene Regulation. Chromatin Structure DNA & protein 1) Nucleosomes DNA & histones...
Chromatin StructureDNA & protein1) NucleosomesDNA & histones (proteins)
DNA wrapped around 8-piece histone bead
Chromatin Structure
2) 30-nm chromatin fiber3) Looped domainsFiber loops around scaffold of nonhistone proteins
4) Metaphase chromosomeFurther folding & coiling to compact
Chromatin Structure
In interphase, compacted chromatin: heterochromatin (not transcribed – proteins can’t reach the DNA)
Non-compacted: euchromatin (is transcribed)
Genomic Organization
Gene RearrangementLoss or shuffling of genomeChange loci of genes in somatic cells
TransposonsIf it “jumps” into middle of a coding sequence, it stops normal function
Itself can be activated if near active promotor
Genomic Organization10% of human genome, but many are retrotransposonsMove by means of RNA intermediate & reverse transcriptase
Process like retroviruses
Control of Gene Expression
Cellular DifferentiationBecome specialized for a functionOnly fraction of genes turned on (3-5%)Regulated at transcription by DNA-binding proteins that receive internal & external signals
Control of Gene Expression
Chemical modification of chromatin also regulates transcription1)DNA methylationAttachment of -CH3 groups to DNA bases (cytosine) after DNA synthesis
Inactive DNA is highly methylated (removing can possibly activate genes)
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)
Control of Gene Expression
2)Histone AcetylationAttachment of acetyl groups (-COCH3) to amino acids of histones
Changes their shape – grip DNA less
Easier to transcribe that section of DNA
Control of Gene Expression3) Control elementsNoncoding DNA regulating transcription
Proximal control elements – promotor
Control of Gene ExpressionDistal control elements (farther away) – enhancersCauses DNA to bend so transcription factors (activators) bound to enhancers can contact proteins of TIC of promoter
Repressors bind to control elements known as silencers (much less common)
Control of Gene Expression
CoordinationNeed to turn genes of related function on or off at same time
No operons like prokaryotesEach 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
Control of Gene Expression4) mRNA Degredation5) Translation initiationBlocked by proteins that bind to 5’ end of mRNA so ribosome cannot attach
Control of Gene Expression
6) Protein processing & degradationAfter translationDuring modification or transport of protein
FYI…To destruct protein, it is marked with a protein ‘tag’ (ubiquitin); proteasomes recognize this & degrade the protein
Cancer
Cancer-causing genes: oncogenesFrom retroviruses
Normal gene – proto-oncogeneNormal becomes cancer in three ways:Movement of DNA within genomeAmplification of proto-oncogenePoint mutation of proto-oncogene
Cancer
Tumor-suppressor genesPrevent uncontrolled growthIf damaged, cancer could resultTypical jobs: repair damaged DNA to prevent improper accumulation
Control cell anchorage (absent in cancer)
CancerGenes often involved:1) ras – mutated in 50% of cancersUses signal-transduction pathwayRas 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)
Cancer
2) p53 gene – mutated in 30% of cancersS-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