dev genetics [mod] 2

8/9/2019 Dev Genetics [Mod] 2

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Genetics

Topics :

I. Genetic Basis ofDifferentiation

II. Control of GeneExpression in

Differentiation

III. Nature of


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organism Single fertilized egg

cell embryo adult Adult cells

trillions (1012)

organs Organ tissues

Tissue


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Cell

Differentiation


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Embryo

nic

development

A

mphioxus


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Differentiation

(specialized characteristics)

type Specialized cellular functions

1) Proteins : structuralproteins for cell shapes


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Pathway

Mutation Developmental pathway

differentiation

tissues organs

Phenotypes


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Developmentalpathway

Different gene products

Signal molecules : signalreceptors

Cytoplasmic proteins : signaltransducers

Transcription factors

Regulator proteins


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as s

of

Differentiatio

n


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Differentiation

1. Theory of development

1.1 Theory ofMosaicDevelopment1.2 Theory of

Regulative Development2. Substances ofdevelopment

2.1 Determinants


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Differentiation

Early embryonic cells:

Differentiated cells : specialized products 2 1) Fundamental proteins (vital) Housekeeping genes : RNApolymerases &

ribosomal proteins


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1. Theory of Development

2 Expression genes development

gene express gene express

1.1 Theory ofMosaicDevelopment


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Development

Differentiation embryoniccells geneticpotential

cell cycledevelopment genetic material -->

organism


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Genes

genes potential differentiation

1. Housekeeping genes 2. Luxury genes invertebrate

embryo 2 programmed

differentiate


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Development

embryo eukaryote

8 cells

8 develop 8

organisms 8

(regulated)

Totipotent


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embryo geneticmaterials

3 cell division cycles

mosaicdevelopment

Regulativedevelopment

embryo humans


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totipotency totipotent stem cells/

precursor cells genetic potential muscle cells nervecells

adult cell 1 toti otent differentiated cells


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: animals & plants

totipotent differentiatedcells genetic material

differentiation genes

cell differentiation cell

differentiation


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2. 1 Determinant

differentiate express specific function Determination

Determination point of no return irreversible commitmentDevelopment program fate


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Gradient ofdeterminationsdeterminants

egg

(gradient) -->


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Determinants M

aternalmessages

mRNA egg (developing egg)

Determinants Transcription factors

egg


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2.2 Inducers

Substance

Signal

cell

cell

embryo 3 Mesoderm

induce development


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2.3Morphogens

subsets determinant

inducer Morphogen (morphology) embryo

Morphogen embryo

transplantation


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Retinoic acid morphogen

Retinoic acid hormones differentiation


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II. Control of GeneExpression

in

Differentiation


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Differentiation

Differentiation turn-on

genes

control structural gene

expression

Transcription,Posttranscription,Translation Posttranslation


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Control Prokaryote

gene expression cellularactivity

bacteria Sporulation--> Vegetative

sigma (W) factor


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Control Eukaryote

Expression luxurygenes

1. Hormoneactivation of genes

2. Hormone-


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1. Hormone Activation on Genes

Hormone turn ontranscription

specific genes

target cells1.

genes nucleus2. secondmessengercellmembrane cytoplasm


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Steroid Hormone

Steroid hormone development differentiation

Steroid hormone cellmembrane

cytoplasm

nucleus receptornucleus

Hormone-receptor complex


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Effect

Steroid

Hormo

ne GeneExpres

sion


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Ovalbumin Gene

chick oviduct

estrogen-receptor complex binding site 250-300base pairs upstream TATAbox

hormone-receptor complex transcription factorbind stimulate enhancergene


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receptor

nucleus

development1) Glucocorticoid receptor :

mediate genehormone cortisol

2) Vitamin D3 receptor

3) Thyroid hormone receptor

4) Retinoic acid receptor

Response


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Elements (HRE)

Enhancer receptor

hormone hormone-receptor complex Enhancer

Promotor gene RNApolymerase transcription gene


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Retinoic acid responsive element

(RARE)

binding site DNARetinoic acid receptor (RAR)

RAR

Finger protein2 Zinc fingers


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Retinoic acid receptor (RAR) =

protein

Retinoic acid responsive

element (RA

RE)= DNA sequence RAR-RAREcomplex DNA

Retinoic acid (R) RAR-RARE complex

RA

R-RA

RE complex


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Action Retinoic AcidRAR (receptor) + RARE (element)

RAR-RARE Complex /----Promotor-----Gene-----/

/-------RAR-RARE-

Promotor-----Gene-----/


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receptor (THR)

RARE enhancer Thyroidhormone receptor (THR)

thyroid hormone retinoic acid

growth hormone thyroid hormone receptor

RAR dimer growth-->


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Vitamin D3Receptor

Vitamin D3

Retinoicacid

VDR RAR RARE

turn on Osteocalcingene --> product differentiation immature


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response hormone

hormone receptorspecificity

Hormones target 2-3 cell types Retinoic acid vertebrate

receptor3 types type RARE


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genes

(Seedling)

photosynthetic

apparatus chlorophyll

seedling enzyme chlorophyll light-activated enzyme Ribose bi hos hate carbox lase


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Rubisco Gene

Rubisco gene light-inducible genes

Promoter : -35 base pair region TATA box Sequence -35 -46 light

dependent -46 upstream

Enhancer :- -


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response gene

(a)Rubisco gene

peacloned

petunia cells

(b)

C t l E i


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Control Expression gene cell differentiation plants

animals

Regulatory region / 5-flanking

region cis-acting DNA Control

region structural gene TATA box GC box

-


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III. Nature of

Determination


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Determination

cell

developmental pathway

Chromatinfactor histones

control regions genes


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Determination

1. DNase

Hypersensitivity

2. Control expression

5S

rRNA

3. DNA methylation


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1. DNase Hypersensitivity

DNA Nucleosomes(300 bp) chromatinhistones DNas DNase hypersensitive site


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DNase hypersensitive region 5-flanking region / regulatory region(promoter & enhancer)

turn on/off genefactor (protein) hypersensitivity Nucleosome globin gene Hypersensitivity region 60-260

upstream

nucleosome embryo 14


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expression

5S rRNA genes () 20,000genes 2 family

1. Oocyte 5S rRNA genes : 98 % ,

transcription oocytes

2.S

omatic5S

rRNA

genes : 2 % ,


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families

replication celldivision transcription factors RNA Pol III

factors TFIIIA, TFIIIB, TFIIIC

histones hypersensitivity region

immature egg


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immuture egg: Oocyte 5S rRNA genes

express somatic 5S rRNA genes

repressed developing embryo:Embryo

~3,200 cells

TFIIIA 1/ oocyte rRNA gene

rRNA n


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3. DNA methylation

Active genes low methylgroups Methylation DNA repress gene

signal DNA

methylation

methylation higher


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Determination mehtylation

1) Repress gene activity 2) permanent

Epigenetic mechanism methylationgenetic

gene turn off

development X chromosome female

methylated develop Inactive X chromosome


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Determination

mutation:

genes determination Homoeotic genes

Homeotic genes mutation

(transformation)


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Antennapedia (Antp) mutant

genes cells cells develop programmed develop Transformation activity genes gene

mutated transformation


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Homeotic gene Mastergene

determination

(fate) mutate gene

determination /program Homeotic genes

development Homeotic gene 2 A

ntennapedia complex (A

NT-


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Homeobox

Common DNA sequence 180 bp

Homeotic genes complex(cluster) genes

Non-homeotic genes transform body part homeoticgenes development


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Homeobox

75 % - 79 % conserved

share control genes develop

code protein DNA-bindingdomain positively charged

protein transcriptionfactor migrate nucleus control region


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genes

vertebrate invertebrate

anterior-posterior bodyaxis express genes cluster

genes express(anterior)


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Maternal Effect Genes

Genes code products egg

products eggpolarity

products effect development body parts

bicoid (bcd) gene ~


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Segmentation genes

Control organization

segments ftz gene segment

segment pair-rule genes embryo

engrailed gene embryo

anterior & posterior


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Vertebrate homeoboxes

sequence homeoboxes vertebrate 95%

genes clusterexpress homeotic genes clusters express

homeotic enes


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homeobox gene vertebrateactive active

differentiation

homeobox proteinsvertebrates Transcriptionfactor Regulatordevelopment embryo

Pit -1 protein


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Pit -1 protein mouse dwarf(dw) gene development

pituitary glands growthhormone, prolactin hormone

thyroid - stimulating hormone Pit-1 multiple effects


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Developmental pathway House keeping genes & Luxury

genes Mosaic development vs. Regulative

development Totipotency vs. Epignetics

Determinants, Inducers &Mophogens Differentiation control in

Prokaryote vs. Eukaryote Animal: Hormone-induced genes &

Hormone responsive element Plant: Light-induced genes

DNA hypersensitivity, rRNA geneexpression, and DNA methylation

dev genetics [mod] 2

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