Epigenetic Regulation In Hematopoiesis

Question 1

Who coined the term “epigenetics”?

Answer 1

Conrad Waddington

Question 2

How did Conrad Waddington define epigenetics?

Answer 2

The branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being

Question 3

What is a pluripotent stem cell?

Answer 3

A cell that can develop into any different cell or tissue type in the body

Question 4

How does epigenetics regulate gene expression?

Answer 4

It regulates gene expression without changing the DNA sequence

Question 5

Are epigenetic alterations permanent or reversible?

Answer 5

reversible

Question 6

What are the mechanisms that mediate epigenetic alterations?

Answer 6

DNA modifications, histone modifications, chromatin remodeling, and noncoding RNAs

Question 7

What essential roles do epigenetic alterations play?

Answer 7

They play roles in DNA replication, repair, and transcription

Question 8

How do epigenetic changes relate to hematopoiesis?

Answer 8

They help explain the gradual loss of lineage potential during differentiation.

Question 9

What effect can epigenetic changes have on genes involved in alternative cell fates?

Answer 9

They may lead to the silencing of these genes

Question 10

How do extrinsic factors influence hematopoietic stem cells (HSCs)?

Answer 10

They coordinate multiple processes essential for HSCs

Question 11

What is controlled for the regulation of gene expression in hematopoiesis?

Answer 11

Multistep processes are controlled to regulate gene expression

Question 12

What factors are required to control hematopoiesis?

Answer 12

Factors that control the cell cycle, metabolism, and epigenetics

Question 13

Why are connections between cell cycle, metabolism, and epigenetics important in hematopoiesis?

Answer 13

They are required for homeostasis

Question 14

What can happen if the balance of hematopoiesis is disrupted?

Answer 14

It can lead to hematopoietic malignancies.

Question 15

What is a chromosome?

Answer 15

A structure in the nucleus made up of proteins and DNA that interact to form chromatin.

Question 16

What is chromatin?

Answer 16

The complex of DNA and proteins that make up chromosomes.

Question 17

What are the two main classifications of chromatin?

Answer 17

Heterochromatin and euchromatin.

Question 18

What is heterochromatin?

Answer 18

Condensed chromatin that is transcriptionally silent.

Question 19

What is euchromatin?

Answer 19

Open chromatin that is transcriptionally active.

Question 20

What are the four main types of epigenetic alterations?

Answer 20

Modifications to DNA, modifications to histones, chromatin remodeling, and non-coding RNA regulation (microRNA).

Question 21

What is the basic unit of chromatin architecture?

Answer 21

The nucleosome.

Question 22

What proteins make up the core histones?

Answer 22

H2A, H2B, H3, and H4.

Question 23

How do histones assemble to form a nucleosome?

Answer 23

Histones exist as dimers and come together to form an octameric nucleosome core.

Question 24

What connects nucleosomes to each other?

Answer 24

A linker histone and a short length of DNA.

Question 25

What are the histone N-terminal domains rich in?

Answer 25

Lysine and arginine residues.

Question 26

What types of post-translational modifications occur on histones?

Answer 26

\Methylation, acetylation, phosphorylation, ubiquitination, etc.

Question 27

How do histone modifications affect DNA?

Answer 27

They alter interactions with DNA and nuclear proteins.

Question 28

What are the two main classes of histone-modifying enzymes?

Answer 28

"Writers" (add functional groups) and "Erasers" (remove functional groups).

Question 29

What are two examples of histone "writers" and their functions?

Answer 29

Histone methyltransferases (HMTs), e.g., Enhancer of Zeste Homolog 2 (EZH2), which methylate histones. Histone acetyltransferases (HATs), which add acetyl groups to histones.

Question 30

What are two examples of histone "erasers" and their functions?

Answer 30

Histone demethylases (HDMs), which remove methyl groups from histones. Histone deacetylases (HDACs), which remove acetyl groups from histones.

Question 31

What is DNA methylation?

Answer 31

A process that adds a methyl group to cytosine to form 5-methylcytosine.

Question 32

Are DNA methylation changes static or dynamic?

Answer 32

dynamic

Question 33

How is DNA methylation linked to stem and progenitor cell differentiation?

Answer 33

It involves methylation gain or loss at gene promoters or other regulatory regions (e.g., enhancers).

Question 34

What are the key DNA methyltransferases (DNMTs) and their functions?

Answer 34

DNMT3A: De novo methyltransferase DNMT3B: De novo methyltransferase DNMT1: Methylation maintenance

Question 35

What is the function of DNMT1 in hematopoiesis?

Answer 35

DNMT1 maintains DNA methylation, ensuring efficient hematopoietic differentiation and cell cycle regulation.

Question 36

Q: How does DNMT1 influence stem cell progression?

Answer 36

It plays a crucial role in the transition from stem cells to multipotent progenitors to lineage-restricted myeloid progenitors.

Question 37

What enzymes are responsible for methylation at unmethylated regions?

Answer 37

DNMT3A and DNMT3B.

Question 38

How do DNMT3A and DNMT3B function together?

Answer 38

They show complementary methylation patterns.

Question 39

What happens when DNMT3A is lost?

Answer 39

Loss of DNMT3A leads to hematopoietic stem cell (HSC) expansion by decreasing differentiation and upregulating self-renewal genes.

Question 40

How does the loss of DNMT3A contrast with the loss of DNMT1?

Answer 40

While DNMT3A loss increases self-renewal and reduces differentiation, DNMT1 loss disrupts hematopoietic differentiation.

Question 41

What is the function of Ten-eleven translocation 2 (TET2)?

Answer 41

TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation.

Question 42

What happens when TET2 is lost?

Answer 42

Loss of TET2 leads to a bias toward myeloid lineage differentiation and limits HSC self-renewal, similar to DNMT3A loss.

Question 43

What are cancer stem cells (CSCs)?

Answer 43

A subset of tumor cells that display both cancerous and stem cell properties.

Question 44

How do CSCs divide?

Answer 44

They are quiescent and divide asymmetrically to produce both differentiated and stem-like cancer cells.

Question 45

How do CSCs become more malignant?

Answer 45

They shift from asymmetric to symmetric cell division.

Question 46

What is one proposed model for CSC origin?

Answer 46

CSCs originate from normal stem cells that acquire cancer characteristics.

Question 47

How does epigenetic reprogramming relate to CSCs?

Answer 47

It influences and aids in the formation of CSCs.

Question 48

Which signaling pathways are heavily impacted by epigenetic reprogramming in CSCs?

Answer 48

Wnt, Notch, and Hedgehog (Hh) pathways.

Question 49

What is hemoglobin?

Answer 49

A protein inside red blood cells that carries oxygen and carbon dioxide.

Question 50

What is the primary function of hemoglobin?

Answer 50

To transport oxygen from the lungs to tissues and organs and return carbon dioxide to the lungs.