Epigenetics

Question 1

6 steps to control eukaryotic gene expression:

Answer 1

transcriptional control, RNA processing, RNA transport, translational control, mRNA degradation, and protein processing

Question 2

Most Epigenetics takes place during ____ control

Answer 2

Transcription

Question 3

_____ is heritable changes in gene expression that don’t involve changes to the underlined DNA sequence. Change in phenotype without change in genotype

Answer 3

Epi-genetics

Question 4

Epigenetic change is a ___ and ____ occurrence but epigenetic change is influenced by factors like age, environment, and disease state

Answer 4

Regular and natural

Question 5

Normal functions of epigenetics include:

Answer 5

Cell differentiation, maintenance of genome structure, suppression of repetitive elements in invasive DNA, dosage compensation between XY and XX, and genomic imprinting

Question 6

______ is a set chemical modifications to DNA and DNA associated proteins which alter gene expression and are heritable via meiosis and mitosis.

Answer 6

Epi-genome

Question 7

DNA methylation and histone modification are common ____ of Epigenetics

Answer 7

Mechanisms

Question 8

Euchromatin is associated with ____ DNA versus heterochromatin is associated with _____ DNA

Answer 8

Unmethylated
Methylated

Question 9

The DNA _____ state is inherited

Answer 9

Methylation

Question 10

_____ at histones promotes Euchromatin

_____ at histones promotes heterochromatin

Answer 10

Acetylation
Phosphorylation

Question 11

When a methyl group is added to a ____ in DNA, this promotes heterochromatin and gene silencing

Answer 11

Cytosine

Question 12

_____ ____ are CpG sequences 200 to 1000 base pairs.

_____ CpG islands are in/near promoters of active genes 60 to 70% of promoters have CPG islands.

_____ CpG islands are within large repetitive sequences and in intergenic regions they are next to genes that are silenced in a specific tissue

Answer 12

CpG islands
Unmethylated
Methylated

Question 13

Cytosines are methylated by ___ ____ at the five carbon. _____ is a type of DNA methyl transferees that maintains existing methylation patterns following DNA replication. _____ and ____ target previously unmethylated CpGs they are highly expressed in the embryo during implantation and establish new methylation patterns

Answer 13

DNA methyltransferases
DNMT1
DNMT3A and DNMT3B

Question 14

CpG represents a _____ DNA sequence when it is double stranded making it easy for it to be recognized and inherited

Answer 14

Palindromic

Question 15

_____ _____ is when new DNA strands are not methylated during DNA replication, the methylated DNA gets diluted out as the cell or embryo goes through multiple cell divisions

Answer 15

Passive demethylation

Question 16

____ ____ is by so-called TET (ten-eleven translocation) enzymes

Answer 16

Active demethylation

Question 17

Answer 17

Question 18

____ is a process by which some genes are epigenetically silenced during game to genesis in a parent of origin specific manner, which results in only one ____ being expressed for the imprinted loci

Answer 18

Imprinting
Allele

Question 19

The main mechanism of epigenetic imprinting is ____ ____

Answer 19

CpG methylation

Question 20

The fertilized ovum is ____ meaning it has the potential to become an entire organism and to make the placenta tissue

Answer 20

Totipotent

Question 21

Epigenetic modifications during development determines ___ ____ and feet by limiting the developmental potential of individual cells and their progeny

Answer 21

Cell differentiation

Question 22

The zygote must have many prior epigenetic marks ____ because both the eggs and Sperm had genomes of specialized cells: ____ and ___
Now we have to be able to make all cell types

Answer 22

Erased
Spermatozoa and oocytes

Question 23

Zygote genome has both male and female imprinted marks from paternal and maternal chromosomes, marks need to be erased so that ____ ___ of gametes based on its own genotypes can be expressed. It also needs to be _____ silent

Answer 23

Sexual determination
Transposons

Question 24

Epigenetic reprogramming occurs at two different points during development:
1. In the ____ before the blastocyst stage
2. In the ____ ___ ____ within the developing embryo

Answer 24

Zygote
Primordial germ cells (PGCs)

Question 25

In the zygote, the maternal and paternal genomes undergo ___ ____ resetting the genome for totipotency (ability to make all cell types) at the ____ stage.

Answer 25

Global demethylation Blastocyst

Question 26

There is another round of global demethylation during migration of the ____ ____ ___. It’s thought that most imprinted alleles are not erased so that there are parent specific ____ patterns

Answer 26

Primordial germ cells Methylation

Question 27

Need to be able to equalize the gene expression in individuals with 2X compared to those with one X. Change the gene _____ by _______. The X gets condensed down into a ____ ____. This is called _____

Answer 27

Regulation X inactivation Barr body Lyonization

Question 28

X inactivation is initiated by a ___ _____ ___ called Xist. Xist is transcribed from the __ ______ ____ of the chromosome to be silenced. Xist coats Xi and serves as a scaffold for modifying enzymes.

Answer 28

Long non-coding RNA (lncRNA) X inactivation center (XIC)

Question 29

Xi displays _____ histone modifications and DNA methylation Xa displays _____ modifications Somehow, XIC senses the number of X chromosomes and ____ silenced one

Answer 29

Repressive Activating Randomly

Question 30

_____: heritable change in gene activity not associated with a DNA sequence change. Results from _____ changes, or defects in epigenetic control mechanisms that cause deregulation

Answer 30

Epimutation aberrant

Question 31

Epimutations affect many aspects of human health including ____ and ___ health

Answer 31

Metabolism Mental

Question 32

Epimutations can drive carcinogenesis, 20% of sporadic breast cancers display ____ of the BRCA1 promoter

Answer 32

Hypermethylation

Question 33

Epigenetic deregulation on a molecular level:

Question 34

Epigenetic inheritance: Week 3 of gestation, primordial germ cells are already forming, thus the babies future gametes can be _____ exposed to an epigenetic event

Answer 34

Directly

Question 35

_____ _____: transmission of an induced trait from one generation to another without direct exposure

Answer 35

Transgenerational inheritance

Question 36

______ _____= prenatal exposure: the mom (F0) is exposed while she is pregnant. The child’s (F1) somatic cell epigenome is programmed by the exposure but not it’s germline. The grandchild (F2) are unaffected. Direct exposure of the F1 child

Answer 36

Intergenerational inheritance

Question 37

_______ _____: the child (F1) is exposed during gestation and so are the child’s developing germ cells (F2). The grandchild (F2) will have a phenotype but does not pass it to his/her own children (F3) because those gametes are reprogrammed back to normal during development. Direct exposure of the F2 child

Answer 37

Multigenerational inheritance

Question 38

______ _____: the F1 gametes are modified during gestation so the F2 child is affected. If these marks are not erased during PGC differentiation, F2 gametes remain affected and the F3 generation has the altered phenotype. Indirect exposure

Answer 38

Transgenerational inheritance

Question 39

The evolution of metabolic epigenetic marking is thought to enhance ____ ____ by programming energy balance so that available nutrients are used most efficiently

Answer 39

Offspring survival

Question 40

Metabolic epigenetic marking allows for quicker adaptation to the environment than ____

Answer 40

Evolution

Question 41

Metabolic epigenetic marking is the programming of an offspring’s future metabolic responses by a stimulus that occurs during ____ ____ ____

Answer 41

Critical embryological periods

Question 42

Example of metabolic epigenetics is maternal diet of mice can affect the ____ of the offspring. It takes 3 generations of a normal maternal diet to reverse these changes

Answer 42

Length

Question 43

Women who were pregnant in the Dutch hunger winter famine only ate 400 to 800 calories per day and delivered low ___ ____ babies. By 50, those offspring had increase BMI, schizophrenia, diabetes. Likely caused by the _____ of the ____ locus compared to their same sex siblings

Answer 43

Birth weight Hypomethylation IGF2

Question 44

Both ____ and _____ of the mother can lead to obese phenotypes

Answer 44

Overnutrition and undernutrition

Question 45

____ ____ ____ is associated with insulin resistance in young adults

Answer 45

Prenatal psychosocial stress

Question 46

____ ____ ____ is associated with offspring having several metabolic syndrome conditions

Answer 46

Maternal holocaust exposure

Question 47

____ ____ during the preconception or prenatal period: offspring at increase risk for developing type II diabetes

Answer 47

Maternal bereavement

Question 48

Hypermethylation of tumor suppressor genes can cause ____. Global genomic ____ where all genes are expressed can lead to cancer. Persistence of ___ ___ inappropriately can lead to cancer

Answer 48

Cancer Hypomethylation m5c Residues

Question 49

Cancer: ____ increase and methylate CpG islands in tumor suppressor genes. It is proposed that ____ decrease and repetitive elements and oncogenes become demethylated

Answer 49

DNMTs DNMTs

Question 50

Many ________ and _____ syndromes are caused by altered or defective function of epigenetic machinery: ability to read, write, erase, and remodel markings. Misregulation of ___ and ____ ____ are common features of disorders

Answer 50

Neurodevelopment Developmental Growth Intellectual disability

Question 51

Imprinting disorders: Beckwith wiedemann syndrome is an ___ disorder, only paternal imprinting present Silver Russell syndrome is an ___ disorder only maternal imprinting present

Answer 51

Overgrowth Undergrowth

Question 52

Imprinting disorders: Prader Willi Syndrome is characterized by ___, ____, and ____. Only maternal imprinting present. Angela syndrome is characterized by seizures ataxia speech impairment. Only ____ imprinting present

Answer 52

Hypotonia, hyperphagia, hypogonadism Paternal

Question 53

Take home message

Answer 53