Epigenetique 1.0: Class Flashcards
What is Chromatine?
ADN + échaffaudage de protéines, incluant:
- facteurs de transcription
- histones
True or False,
La différenciation épigénétique est irréversible
True
But
cancer can activate/innactivate in order to promote survival
Dans le cancer:
Réactivation de gènes normalement inactifs
+
Inhibition de gènes normalement transcrits
Normally, epigenetics -> Marque transmise d’une cellule à toutes ses
descendantes. When is this not true?
Marque effacée dans l’embryon précoce
- déméthylation globale de l’ADN de la morule-> starting over from this point!
The parental imprented cells are not affected
True or False
Marque épigénétique est une altération au niveau de la ADN, contrôlant la
transcription
Altération au niveau de la chromatine, contrôlant la
transcription sans changer la séquence d’ADN
Trithorax vs Polycomb
Histone epigenetic markers
Trithorax: Gene activator
TTX: fonction topoïsomérase
-> Peuvent faire glisser les nucléosomes sur l’ADN (page 38)
Polycomb: Gene inhibitor
TTX active et Pc inhibe la transcription
DNA
Méthyle transférase (DNMT) will methylate what? What is the efect of this PRECISELY??
Méthylation des CG
cytosine guanine
méthylation des CpG peut empêcher la
liaison des facteurs de transcription
avec l’ADN
pg13
acetylation vs deacetylation and DNA transcription
Acetylation is a process where an acetyl functional group is transferred from one molecule to another1. When histones are acetylated, it removes the positive charge on the histones, thereby decreasing the interaction of the N termini of histones with the negatively charged phosphate groups of DNA1. This transforms the condensed chromatin into a more relaxed structure, referred to as euchromatin, that is associated with greater levels of gene transcription1.
On the other hand, deacetylation is the reverse reaction where an acetyl group is removed from a molecule1. This can be catalyzed by enzymes with “histone deacetylase” (HDAC) activity1. Deacetylation increases the interaction of the N termini of histones with the negatively charged phosphate groups of DNA, leading to a more condensed chromatin structure, referred to as heterochromatin1. This is associated with lower levels of gene transcription
MeCP2 clinical relevance
The MECP2 gene is located on the X chromosome, and Rett syndrome is classified as an X-linked dominant disorder2. As a result, males are more severely affected and rarely survive infancy, while females, due to X chromosome inactivation, have a mixture of cells that express either the wild-type or mutant version of MeCP2
Syndrome lié au X, dominant,
♀ : seules les filles sont atteintes
♂ : presque toujours létal chez les hommes
The X is:
hypo-acétylé
hypermethylated
->overactivation of MeCP
role of Histone DeAcetylase (HDAC)?
Recruited by MeCP
It reduces the amount of acetyl
Les histones sont
dé-acétylées par
HDAC, ce qui
inhibe la
transcription
Low Acetyl -> condensed DNA -> hétérochromatine
Met1?
Met1 is an DNA
Méthyle transférase (DNMTequivalent)
however this is recruited via ncRNAs. Specifically, double branded RNA
recognizes a part of the complementary DNA and leads to methylation (via Met1) and thus the inhibition of those genes until death do us appart.
Contrôle
post-transcriptionnel
Dégradation de l’ARN par siRNA
microRNA (from Dicer) leads to the cutting of the RNA and inhibition
RISC takes the segmented RNA that was done by DICER and then binds any complementary RNA found in the cytoplasm and cuts it down
What is the role of dicer?
Cut messengerRNA in small fragments (in the cytoplasm)
(dice your onion)
What is the role of RISC?
Takes the segmented RNA that was done by DICER and then binds any complementary RNA found in the cytoplasm and cuts it down
True or False,
For non coding RNAs to have an effect they must first be translated to proteins.
FASLE,
ARN non-transcrits they can have effect without being proteins
ESCC vs Let-7?
ESCC -> leads to a cellule souche!! (stem cell)
LET-7 -> innactivates molecules in order to keep cell as differentiated
un miRNA peut à lui-seul
transformer une cellule différenciée en
cellule souche.