Epigenetics Flashcards
What does DDT correlate to in terms of genetic difference?
It leads to inheritance of obeisity
What does tighter DNA in mitosis lead to?
Lower expression and transcription levels
Do epigenetic effects have the ability to be heritable?
Yes
How can epigenetics be explained from a stem cell viewpoint?
Epigenetics leads to differentiation of stem cells into different cells.
What are epigenetics?
The study of DNA sequence combined with variable gene expression
What are the 4 most recognized epigenetic regulations?
DNA tagging
Histone Modifications
Non-coding RNAs
RNA modifications (post transcriptional)
What is DNMT and what does it do?
DNA methyltransferase is a family of enzymes that catalyzes the methylation of DNA
What are the three properties of CpG islands?
- They are 200-2000 base pairs long
- They are typically found near promotors of genes
- They play a large role in gene regulation
What is a CpG site?
A cytosine followed by guanine in linear sequence
When does CpG lead to gene expression silencing?
When it is methylated, the genes are silences
Unmethylated = expression
What is the difference in function between DNMT1, and DNMT 2/3?
1 - Preserves methylation pattern during cell division
2/3 - Induces de novo methylation to control differentiation
What can be said about the heritability of histone modifications?
They are inherited through cell division, which can maintain an expression pattern across cell generations
What does de novo DNA methylation include to effect expression?
The methylation of new CpG sites, or increased methylation of a site
What is the mechanism with which DNMT1 adds methyl groups to DNA?
It recognizes hemimethylated DNA and adds methyl groups to the unmethylated strand, ensuring patterns are copied
What is hemimethylated DNA?
It is when one strand is unmethylated
How does methylation interfere with DNA expression?
It interferes with the docking of the TM (transcriptional machinery)
What is transcriptional control by methylation highly dependent on?
location of methylation relative to the gene
What is the difference in expression when different parts of the gene are methylated?
It is repressed if the methylation is near a promotor region or start site, and expression is correlated with methylation of the gene body
What other genetic process is gene body myelination hypothesized to be involved in?
Gene splicing
What are transposons?
They are jumping genes that change their position in the genome
How is DMNT linked to transposons?
Transposons are upregulated in DNMT-1 deficient mice
How are transposons silenced in mammals?
- Bulk de novo methylation of old transposons from DNMT3A/L
- PIWI proteins recruit DNMT3A/L enzymes
What is X chromosome inactivation (XCI)?
A process in female mammals where one of the two x chromosomes is silenced to achieve dosage compensation
When are sexual dimorphisms observed due to DNA methylation?
When there is low methylation on a promotor CpG region of the X chromosome in females.
In terms of histones, what does gene expression depend on?
Nucleosome position, mobility, and packaging
What structure is critical to the knowledge of chromatin properties on gene mechanisms?
The nucleosome core particle NCP
What are the four properties of histones with impact on DNA expression?
- Chromatin structure - condensed or relaxed structure
- Recruitment of regulatory proteins - activate or repress transcription
- Histone code hypothesis - modifications can make a code that regulating proteins read
- Histones are dynamic and reversible
What type of RNA is responsible for epigenetics?
Non-coding RNA, NCRs
What important complex processed NCRs?
The RISC, RNA-induced silencing complex
And AGO protein
What does AGO do?
It loads a small RNA- duplex to make pre-RISC
What is mature RISC?
It is the red (guide) strand of DNA with the blue (passenger) strand ejected
What guides RISC to its complementary RNAs?
small RNA
What three types of ways does RISC use to stop gene expression?
- mRNA cleavage
- degradation
- translational repression
What types of RNA are involved in silencing?
Micro RNA (miRNA) and silencing RNA (siRNA)
What is the process that miRNA takes to get to its RISC form?
pre-miRNA is produced in the nucleus, it is sent to the dicer, which turns it into miRNA, which then is loaded into protein AGO2 to make RISC
What is the process that siRNA takes to get to its RISC form?
double stranded RNA is cut by the dicer and loaded to AGO2 to make RISC
What does siRNA do to mRNA?
Degradation
At what levels do non coding RNA act?
At the gene and chromosome level
How man RNA modifications have been discovered, and what accounts for two thirds of these cases?
More than 170 modifications have been found, with 2/3 of these bring from methylation
What does histone tail methylation do in a 2023 study?
It allows for the control of muscle specific genes during myogenesis
What DNA process is correlated with age?
Methylation of DNA
