Lecture 5

Front 1

Cells maintain their specialised characteristics. Give experimental evidence:

Back 1

- transplanting a nucleus from differentiating muscle into a enucleated egg - many progeny cells express a muscle marker in non-muscle regions;

Front 2

How is gene expression profile passed on from parent to daughter cell?

Back 2

- Cells retain a record of signals their ancestors received during Development

- instead of continuously receiving instructions from the surrounding

Front 3

Hox genes give each cell a permanent record of their A/P position. How?

Back 3

- 2 memory mechanisms

- Hox genes autoactivate their expression

- Trithorax and polycomb groups of proteins - stamp Hox gene chromatin with a heritable record of gene activation or repression; they are key general regulators of chromatin

Front 4

What is the function of Polycomb?

Back 4

- it maintains repressed Hox expression

Front 5

What is the function of Trithorax?

Back 5

- maintain expression of Hox genes

Front 6

What does a mutation in Polycomb cause?

Back 6

- Initially Hox gene expression is normal, but then it becomes switched on all along the A/P axis.

Front 7

How is cell memory set up through a positive feedback loop?

Back 7

- once activated by some external signal, the feedback loop will continually activate itself, even as the cell divides and the signal is taken away.

Front 8

Give an example of how state of chromatin can affect gene expression:

Back 8

- X-chromosome inactivation - early in development one of the two copies is inactivated in a form of heterochromatin;

- done by non-coding RNA called Xist

Front 9

What is the structural organisation of the core histones?

Back 9

histone tails extend from the core

Front 10

What epigenetic marks processes lay markers on chromatin (histone tails) that change DNA expression?

Back 10

- methylation

- phosphorylation

- acetylation

Front 11

What is the job of transcription factors?

Back 11

- they direct local alterations in chromatin structure

Front 12

What are four types in which transcription factors direct local alterations in Chromatin structure?

Back 12

- nucleosome sliding - allsows access of transcription machinery to DNA

- transcription machinery assembles on nucleosome-free DNA

- histone variants allow greater access to nucleosomal DNA

- specific patterns of histone modification destabilize compact forms of chromatin and attract components of transcription machinery

Front 13

Meanings of some histone modifications:

Back 13

Front 14

What are the two main types of epigenetic mechanisms?

Back 14

- cis-acting

- trans-acting

- both are inherited

Front 15

What are the two types of cis-acting epigenetic mechanisms?

Back 15

- DNA methylation

- Histone modification (used by Polycomb and Trithorax)

Front 16

What are the two types of trans-acting epigenetic mechanisms?

Back 16

- positive feedback loop by transcription regulator (simplest most common route)

- protein aggregation state

Front 17

How to embryonic stem cells maintain their cell state?

Back 17

- similar to the way differentiated cells keep their state

- Polycomb is involved

- direct and indirect positive feedback expression of key transcription factors

Front 18

Give examples of when differentiated cell state is not permanent?

Back 18

- Forced transdifferentiation

- heterokaryon experiments

- nuclear and cellular reprogramming

Front 19

What is forced transdifferentiation?

Back 19

- when one mature somatic cell changes into another type of mature somatic cell without undergoing pluripotency stage

- Forcing mouse embryonic fibroblasts to express MyoD was found to be sufficient to turn those cells into myoblasts.