110-1 Final exam question (Epigenetics part)!!!!

and some key notes

Attached below please find the final exam question for you to prepare in advance. I may also try to write
some tips answering these questions. With all other deadlines, I do not know whether I can make it. The
following short notes should give you enough material to elaborate.

Please use your own words to describe your understanding of one of the epigenetic phenomenons. Please try
your best not to leave the answer blank. I leave enough hints and key words in the question itself. You can
understand the question properly, and just say that repressive histone marks are involved in turning
off/turning down the genes that should be repressed and active histone marks are used to up regulate specific
gene expression to achieve that particular physiological (inactivating one X chromosome in mammalian
females; establish cell type specific epigenetic signature and gene expression pattern after differentiation;
causing global gene hyper-activation plus silencing tumor suppressor genes in cancer…..). It shouldn’t be too
hard to get most score for this question.

Introduction:
Epigenetics refer to one layer of transcriptional control, via opening or tightening chromatin structure on
regional genomic regions, usually associated with higher or lower transcriptional activities, respectively.
Epigenetic layers of gene regulation does not change primary DNA sequences, instead introduce DNA
methylation, histone tail post-translational modifications (like H3K4me3, H3K27me3 etc, as active and
repressive marks, respectively), histone variants and some functional non-coding RNAs to make chromatin
structure being more or less accessible to transcriptional factors (TF) and other factors needed for
transcriptional initiation or maintaining an existing transcriptional activities. A very powerful nature of
epigenetic modulation is its reversibility. This is how epigenetic reprogramming that cause genome wide
gene expression profile changes can be observed in physiological (as in germ cell development) or
experimental condition (as in induced pluripotent cell production; somatic cell nuclear transfer). Epigenetic
changes are also observed during cancer formation, with global relaxation of chromatin structure and
regional tightening of specific genomic regions (as in tumor suppresser genes). Since aberrant epigenetic
marks may be reversed or fixed by manipulating epigenetic modifying enzymes, these epigenetic levels of
modulation has been of great interest in pharmaceutical industry to develop new drugs to cure disease or
anti-aging.
Final exam question : (10% of the final exam score)
(Choose just one phenomenon would be enough; 1-9 擇一作答;
任選答一項生理或病理現象即可，描述其中表觀基因體調控機制。
中、英文、中英夾雜作答皆可。 )

Please choose one of the following biological phenomenons to describe how epigenetic level of
modulation is involved to achieve that physiological or pathological phenomenon:

1. During stem cell differentiation, how epigenetic machineries (DNA methylation, histone modifications
etc.) facilitate cell type specific gene expression pattern establishment?

2. Sex chromosome dosage compensation. Taking mammalian species as an example: this refers to X
chromosome inactivation. (non-coding RNA; histone modifications and DNA methylation are all
involved)

3. Aging: Please describe the changes of epigenetic signatures and 3D chromatin structure between young
and old cells

4. Cancer: Please describe the changes of epigenetic signatures between cancer and normal cells

5. Genomic Imprinting: Please describe how non-coding RNA; histone modifications and DNA
methylation coordinated to set up parental origin specific epigenetic marks to control imprinted gene
expression (maternally expressed imprinted genes having the majority of its transcription product from
the oocyte/egg derived copy, while the paternally expressed imprinted genes mainly expressed from the
sperm derived copy)

6. Induced pluripotent stem (iPS) cell production: Please describe how scientists used the “reversibility”
property of epigenetic marks to reprogram a fully differentiated cells back to pluripotent stem cell
(similar to embryonic stem cell status) by several key pluripotent cell enriched transcription factors
(Oct4, Klf4, Sox2, c-Myc, etc)

7. Somatic Cell Nuclear Transfer (SCNT, also called animal cloning, as the example in Dolly the Sheep):
Please describe how scientists used the “reversibility” property of epigenetic marks to reprogram a fully
differentiated cells into zygote (fertilized egg)-like totipotent status, by transplanting a differentiated
somatic cell into an enucleated oocyte (去核卵母細胞）

8. The different phenotypes between identical twins: Please describe how epigenetic is involved in the
different phenotypes (getting particular disease or not) between identical twins that may be caused by
their different exposure to environmental factors (different education system; major traumatic event
heavy metal in drinking water; carcinogens; smoking or not; nutrition status…..)

9. The involvement of epigenetic modulation in any other physiological or pathological phenomenons, as

long as you can convince us, you would get the marks. Some examples include the endogenous
transposable element modulation, epigenetic reprogramming during germ cell development….