Epigentics Flashcards
What are the two important criteria of epigenetic changes?
Clonal and Revesible
What are the changes in DNA sequence that are done by epigenetic?
NO CHANGE IN SEQUENCE
How is the maternal and paternal alleles activity different in epigenetic in contrast to genetics?
Epigenetic - Paternal or Maternal
Genetics - Both on or Both off
Epigenetic modifications can be _______ by offsprings.
Epigenetic modifications can be Inherited by offsprings.
What are the examples for environmental factors that change the epigenome?
Infection, Smoking, Aging, Pollution, Dietary components
Transcriptional Epigenetic mechanisms
DNA methylation
Chromatin Modeling
Post-transcriptional epigenetic general mechanism-
NcRNA
Post translational epigenetic general mechanism -
Histone Modification
What are the targets of DNA Methylation?
CpG Islands
What are the 3 important DNA methylation enzymes?
DNMT1 - Maintenance of methyltransferases
DNMT3A and DNMT3B - De-Novo methylatransferases
Hypomethylated DNA - Consequence?
Genome Instability - Mutation or rearrangements
Hypermethylated DNA - Consequence?
Promoter Silencing
Deamination of Methylated DNA - Consequence?
Mutation - mCpG to TpG
Methylated DNA with UV light radiation- Consequence?
Increased chance for UV-induced mutations
Methylated DNA with carcinogens presence- Consequence?
Carcinogen induced mutation - bind easily to the mCpG
PTMs of Histones
Acetylated
Methylation
Phosphorylation
Ubiquitinated
What is the consequences possible from PTMs of Histones?
Accessibility of Chromatin changes
What are the important targets of Histone modifications? AAs
K - Lysin
R - Arginine
What are the different groups of Histone modifying proteins?
Erasers
Writers
Readers
Histone code Hypothesis
Different combinations of histone modifications (especially next to promotor) may be very specific to the transcriptional state of that gene.
Chromatin states
Active, Permissive, Repressed, Inactivated
What are the two basic kinds of epigenetic ncRNA?
Long ncRNA - >200 nt
Short ncRNA - < 200 nt
RNA interference (short ncRNA) - Prevention of Translation
Gene inactivation (Post-transcriptional, Dicer, RdRP) may be due to endogenous virus, transposing and retroviruses
MicroRNA (short ncRNA) - Prevention of Translation
20-23 long RNA with RISC navigation to the gene is leading to mRNA degradation or inhibition of translation depending on the complementary match quality.
LncRNA are causing prevention of (2) -
Transcription
Translation
What is possible for a regulation mechanism of LncRNA with Protein?
All levels of gene expression regulation
X chromosome inactivation - dose compensation
Equalize the expression of genes between members of different biological sexes.
Barr body generation.
XIST
X-inactivated specific transcript
A Long ncRNA transcribed from the X chromosome to be silenced by the same XIST
Steps of Barr body formation
XIST expression Histone modification Late DNA replication MacroH2A incorporation DNA Methylation
Types of X chromosome inactivations (XCIs)
Random XCI - healthy normal
Skewed fortunate XCI- mostly normal
Skewed unfortunate XCI - mostly mutant
Male XCI - only mutant
What is the process that allows for chromosome counting and choice of XCI?
Cell Division
Autoimmunity and XCI - The connection
Thymocytes XCI could cause skewed expression of X linked antigens - T cell maturation alteration.
Genomic imprinting
Non-equivalent expression of genes on parent of origin
Gynogenote and Androgenote
Total maternal and paternal forms of fertilized egg not viable for implantation
Prader- Willi Syndrome - causes
Maternal UPD
Paternal deletion of 15q11-13
Wrong imprinting
Angelman Syndrome - Causes
Paternal UPD
Maternal deletion of 15q11-13
Wrong imprinting
UBE3A mutation
What are the imprinted genes number normal?
Around 100
What is the function of the imprinted genes?
Growth or, and Behavior
What are the paternal and maternal genes aim in imprinting in relation to growth (different for each)?
Maternal - silence growth promoting genes
Paternal - silence growth reducing genes
What are the species that present gnomic imprinting ?
Mammals only
Loss of imprinting
Instead of mono-allelic expression, abnormally biallelic expression or total silencing in cancer!
