What is epigenetics?

Question 1

What occurs primarily at CG sequences? What are CpG islands?

Answer 1

• Transcription of most protein coding genes in mammals is initiated in promoter-rich CG sequences (where cytosine is positioned next to a guanine nucleotide linked by a phosphate. Stretches of CpG-dense DNA are known as CpG islands.

Question 2

How does methylation affect chromatin structures adjacent to CpG islands?

Answer 2

Methylated CpG structures impart tight compaction to chromatin, preventing onset of transcription and thus gene expression.

Question 3

What is histone?

Answer 3

Histones are proteins that bind around DNA, condensing and structuring the DNA of eukaryotic cell nuclei into nucleosomes. Histones are the main component of chromatin, without which the molecule would be 40000x longer.

Question 4

What are the functions of chromatin and chromatin modifiers??

Answer 4

Chromitin = DNA + histones. Chromatin modifiers are groups of proteins that bind to DNA, adjust conformation and modify histones in order to influence gene.expression.

Question 5

What is the role of histone tails?

Answer 5

N-/C-terminus histone tails are a common site of post-translational modification (generally acetylation in regions of active transcription), which has immense influence over the degree of chromatin compaction, and thus transcriptional activity/silencing.

Question 6

Are these processes independent? (DNA methylase –> histone modifier –> chromatin remodelling)

Answer 6

No, all three remodelling processes work together and significantly interact in their recruitment. This “cross-talk” is multidirectional and multimodal. For example, DNA methylase can recruit a histone modifier, which can in turn recruit chromatin remodelling complexes.

Question 7

What are the two stages of global epigenetic reprogramming of toti- and pluri-potent cells and when do they occur?

Answer 7

Global demethylation/remethylation of histone posttranslational modifications.

1. When gametes fuse to form the zygote (gametogenesis).
2. When primordial germ cells (gamete precursors) develop and migrate within the embryo (embryogenesis).

Question 8

Does every gene undergo epigenetic reprogramming?

Answer 8

No, around 1% of genes are imprinted, retaining epigenetic tags by entirely bypassing reprogramming.