Lecture 42: Epigenetics Flashcards
Euchromatin
Heterochromatin
Euchromatin
- Decondensed
- Transcriptionally active
- Increases w acetylase (Enzyme: HATs)
- Neutral charge
Heterochromatin
- Condensed
- Transcriptionally inactive
- Increases w deacetylase of histones (Enzyme: HDACs)
- Decreases + charges
What does DNA methylation do and how does it work?
-Modifies cytosine to 5-methyl-cytosine =TRANSCRIPTIONAL REPRESSION in next generation
Process:
1) Unmethylated DNA –> (dnmt3) methylates –> methylated DNA
2) MeCP2 recruits either HDAC1 or Dnmt1
3) HDAC1 deacetylates histones
4) Dnmt1 methylates hemimethylated DNA
Step 4: *Must use MeCP2 and Dnmt1 again to keep newly synthesized daughter strand of DNA methylated
Immunodeficiency-centromeric instability-facial anomalies syndrome (ICF)
Cause?
AR disorder
Cause:
MUTATION IN Dnmt3b
-Instability of chromosome 1, 9, 16
Symptoms:
- Mental retardation
- facial dysmorphism
- prolonged infections
- Decrease of IgA
Retts Syndorme
- MUTATION in (MeCP2) of X-linked gene
- Rarely occurs in boys
Symptoms:
- Loss of speech/hand skills
- Seizures
- Repetitive hand movements
- Irregular breathing
- Motor control problems
Embryonic human blood stem cells and DNA methylation
- Switching of globin chains of hemoglobin occurs in fetal development
- Switching regulated by CHANGES in DNA METHYLATION of control regions (located in promoter of genes, these encode for diff globin proteins)
Genomic imprinting
Basic idea
- Inequal contribution from parents (Violates mendels law)
- Only moms or dads copies of genes are expressed
- Maternally imprinted= moms copy shut off
- Paternally imprinted = dads copy shut off
- whichever is shut off wont be expressed in the offspring
-Can give us the wrong idea if a disease is D or R
Gene Imprinting and Gametogenesis
-Imprinting occurs in gametogenesis that causes mom or dads genes to be shut off
Gametogensis Process:
1) Primordial germ cells enters gametogenesis = Genetic imprint erased
2) Male (in sperm) and female (in oocyte) imprint established
3) After fertilization genome hypomethylates, but imprinted genes remain methylated
4) Methylation increases in development and cell differentiation
Prader Willi Syndrome
Angelman Syndrome
- Subject to genomic imprinting
- Chromosome 15
Prader willi
-Dads genes (SNRPN) imprinted or deleted
Angelman:
-Moms genes (UB3A) imprinted or deleted
Decitabine
-Bind to methyl-transferase enzymes and inhibit methylation of cytosine (which is needed for transcriptional regulation)
Reduces overall methylation
5-Azacytidine
-Bind to methyl-transferase enzymes and inhibit methylation of cytosine (which is needed for transcriptional regulation)
Reduces overall methylation
Beckwith-Wiedemann Syndrome (BWS)
Cause:
- Maternal chromosomal rearrangements of 11p15 (imprinting region)
- Paternal disomy (UPD)
- Abnormal methylation at 11p15
Symptoms:
- Macroglossia (enlarged tongue)
- Large birth weight
- Abdominal wall defects
- Ear crease
- Natal hypoglycemia
IVF:
-One band = one copy lost its imprinting
Environmental factors that effects how genes are expressed in offspring
1) Site of fertiziliation
2) Toxic
3) Maternal care
4) Diet
5) Hypoxia
6) Stress (Ex: glucocorticoid receptor)
Identical twins genetics
- Similar at birth
- Change as they age due to epigenetics
Gemete Theory of transgenerational epigenetics
- Environmental exposures effects generations 1 (mother), generation 2 (fetus), and generation 3 (offspring)
- Grandma can screw us all over
Incontinentia Pigmenti
Cause:
-Mutation of the X-linked IKBKG gene
“I Know Back Kinda Gross”
Symptoms:
-Marble cake on yo back
