Eukaryotic Gene

Regulation

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