Gene expression

Question 1

Difference between Heterochromatin and Euchromatin?

Answer 1

Heterochromatin is heavily condensed, gene poor with silent genes, and replicates late in the phase. The DNA is hypermethylated, and rich in H1, being repressive and have post-translational marks.
Euchromatin in less condensed, gene rich and has active genes. It is replicated early in phase and the DNA is hypomethylated. Histones have specific regulatory post-translational marks

Question 2

What are Polycomb and Trithorax groups and what do they do?

Answer 2

PcG and TtrxG are epigenetic regulators of genome function. PcG silences genes while Ttrx activates genes. They are strongly conserved throughout evolution, maintaining fates of differentiated cells, allowing cell proliferation and x-inactivation in females.
SC maintenance and plasticity
Differentiation
X-chromosome inactivation
Genomic imprinting
Cancer
Cell fate determination
Proliferation

Question 3

How does PcG work?

Answer 3

PcG proteins bind to specific DNA elements called PREs (Polycomb Repressive Elements). They maintain silencing from one cell to another, enhanced by multiple PREs.
PRC2 complex represses developmental genes in mESCs, allowing fine control and essential for early embryogenesis and ESC differentiation.
PRC1 complex catalyses monoUb of histones H2A implicated in Pol II. It pauses mESCs.
Associated with the EZ and PRC1 complex for histones

Question 4

How does TtrxG work?

Answer 4

The MLL complex H3K4 methyltransferase counteracts activity of PcG proteins. It is essential for cell fate transitions in neuronal and haematopoietic lineages.
Associated with the TAC and ASHI complex for histones

Question 5

Why have histone modifications?

Answer 5

Reversible histone modifications allows for rapid changes in gene expression without need for multiple rounds of DNA replication. Enables appropriate responses to developmental cues. Loss of many can result in embryonic lethality.

Question 6

Bivalent chromatin?

Answer 6

Chromatin in a poised state, with both PcG and TtrxG bound. This can be changed form bivalent to univalent mark depending on direction of lineage. Occurs in pluripotent to multipotent transition.