Chapter 2 Meneely: Genomes, Chromosomes, and Epigenetics Flashcards
modENCODE
Encyclopedia of DNA Elements
The modENCODE Project will try to identify all of the sequence-based functional elements in theCaenorhabditis elegansand Drosophila melanogastergenomes.
Genome:
The complete set of genes or genetic material present in a cell or organism.
modENCODE project, summarized
1) extract DNA
2) microarray or sequence
3) salt fractionation
4) chromatin immune precipitation (ChIP)
5) generate antibodies or tagged lines
Epigenetics
The study of heritable changes in gene expression (active versus inactive genes) that does not involve changes to the underlying DNA sequence
A change in phenotype without a change in genotype — which in turn affects how cells read the genes.
Associated gene silencing
histone modification
DNAmethylation
non-coding RNA, e.g., miRNA, siRNA
PEV: Position effect variation
Position eect variegation is an epigenetic change
X inactivation
X-inactivation in calico cats
Xist (X-inactive specific transcript)
is a non-coding RNA on the X chromosome of the placental mammals that acts as a major effector of the X-inactivation process.
Xist is exclusively expressed from the inactive X (Xi) and accumulates on it, leading to a chromosome-wide inactivation of gene expression.
Tsix
is a non-coding RNA gene that is antisense to the Xist RNA. Tsix binds Xist during X chromosome inactivation. The name Tsix comes from the reverse of Xist, which stands for X-inactive specific transcript.
Tsix, with its repressive effect on Xist expression, is expressed normally from the active X and is silenced on Xi.
Features of epigenetic
- DNA sequence unaltered
- affects regions of chromosomes
- stably transmitted
- observed in physical state of chromatin
- associated with IncRNAs
DNA Packing
DNA & 8-pack core of histones
Nucleosomes and the structure of chromosomes:
chromosome –> solenoid chromatin fibre –> DNA –> core histones –> Histone H1 –> nucleosome –> DNA helix
The histone tails
Different residues are sites for possible modification
Modifications of the tails generally are not in contact with DNA
Amino acids available for chemical modification
Closed vs open chromatin
Chromatin can be open or closed, depending on how tightly packed the nucleosomes are
Closed: refractory to transcription factor binding
Open: available for transcription factor binding
Summary of histone modifications
- Methylation (Arginine)
- Methylation (active lysine)
- Methylation (repressive lysine)
- Acetylation
- Both methylation and acetylation
- Phosphorylation
- Ubiquitylation
