Summary
Dosage Compensation Full Summary
- Institution
- University Of Cape Town (UCT)
In depth notes covering the dosage compensation module
[Show more]
Content preview
Epigenetic Regulation of Gene ExpressionCase Study: Dosage Compensa2on
WHAT IS EPIGENETICS
= Heritable changes in gene func2on that don’t involve changes in the gene/DNA sequence
• Study of mito2cally and meio2cally heritable changes in gene func2on that cannot
be explained by changes in the DNA sequence
• 2 major mechanisms
o Methyla2on
o Modifica2on of histone proteins
• Mechanisms modulate transcrip2onal poten2al of genes (regula2on of gene
expression)
METHYLATION IN EUAKRYOTES
• Forma2on of 5 methylcytosine via DNA methyl transferase
• Occurs in CpG islands
o Found upstream in regulatory regions in eukaryo2c genes
o Associated with repression of transcrip2on
GENOMIC IMPRINTING
• Major tenet of Mendelian Gene2cs à origin of allele does not affect its func2on
o Both parents contribute equally to inheritance
o Reciprocal crosses yield iden2cal results
§ Heterozygotes do not display recessive traits
• NOT true for X linked genes in mammals à dosage compensa2on
• Small number of autosomal genes = excep2ons to this rule
o DNA methyla2on of either paternal or maternal allele (genomic imprin2ng)
Eg. Prader Willi & Angelman Syndrome
• Result of deel2ons in the q11-13 region of chromosome 15
• If maternal chromosome dele2on à Angelman syndrome
• If paternal chromosome dele2on à Prader Willi syndrome
• Leads to loss of 2 genes from chromosome 15
o UBE3A = ubiqui2na2on of proteins
o SNRPN = involved in proteins encoding proteins involved in pre-mRNA splicing
• Ordinarily, maternal SNRPN is methylated and paternal UBE3A is methylated
o Humans are hemizygous for these two genes and hence why dele2ons are
causa2ve agents of the two syndromes
o Done in order to prevent genomic conflict
§ Allows for resource alloca2on depending on demands of the individual
o Methyla2on of these genes only resets in germline produc2on
, HOW DOES METHYLATION BLOCK TRANSCRIPTION
• Transcrip2on factors read DNA via major groove and recognize asymmetric paderns
of hydrogen bond donors and acceptors
• Addi2on of methyl groups prevents binding of transcrip2on factors or recruits
chroma2n remodeling proteins to change the structure of chroma2n to prevent
binding
• NB does not interfere with H bonds between bases
1) Addi2on of hydrophobic methyl group alters the ability of certain TFs
2) Recruits MBD proteins to recruit chroma2n remodeling proteins to form repressive
chroma2n
*methyla2on ofen leads to repression of gene expression but it can lead to increased gene
expression!
CHROMATIN STRUCTURE
• DNA = complexed by histone proteins (H2A, H2B, H3 and H4) into nucleosomes
linked by H1 (linker protein)
• Nucleosomes condense to form chroma2n
Condensed chroma2n = repressive (heterochroma2n)
Open chroma2n = permissive (euchroma2n)
à chroma2n packing = dynamic
• Centromeres and telomeres = cons2tu2ve heterochroma2n (always 2ghtly packed)
• Faculta2ve heterochroma2n
o Barr bodies in mammals
o Around one or two genes at a 2me one can pack the chroma2n closely
• Repressive chroma2n prevents accessibility of GTFs and thus RNA pol binding + TIC
forma2on
POST TRANSLATIONAL MODIFICATIONS OF HISTONE TAILS
• Tails of histones protrude from nucleosome
• Most common = acetyla2on and methyla2on
o Performed by acetyl transferase and methyl transferase enzymes
§ Markers are recognized by chroma2n remodeling proteins
• Different markers are recognized by different proteins
• Can have ubiqui2na2on and phosphoryla2on
• Lysine and arginine = most common residues modified (posi2vely charged residues)
• Different regions of the chromosome have different modifica2ons
o Leads to open or closed chroma2n
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through EFT, credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying this summary from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller erinsnotes. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy this summary for R50,00. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
73216 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy summaries for 14 years now