Epigenetics

Question 1

Epigenetic Trait

Answer 1

Stable, mitotically and meiotically heritable phenotype that results from changes in gene expression without alterations in the DNA sequence

Question 2

Epigenetics

Answer 2

Study of the ways in which these changes alter cell- and tissue-specific patterns of gene expression

Question 3

Epigenome

Answer 3

Refers to the Epigenetic state of a cell

Question 4

Epigenetics have been implicated in:

Answer 4

• Progressive restriction of gene expression during development
• Allele-specific expression in gene imprinting
• Environment genome interactions during prenatal development that affect adult phenotypes

Question 5

Abnormal regulation of the epigenome leads to human genetic disorders such as:

Answer 5

Prader-Willi syndrome, Angelman syndrome, and Beckwith-Weidemann syndrome

Question 6

Epignetic changes occur through three major mechanisms:

Answer 6

Methylation: reversable; addition or removal of methyl groups

• Histone modification and chromatin remodeling: alter the accessibility of genes for transcription
• Non-coding RNA

Question 7

Methylation

Answer 7

• DNA takes place after replication and during differentiation of adult cells
• Addition of a methyl group catalyzed by methyltransferase enzymes
• Occurs on cytosine bases adjacent to guanine called CpG dinucleotides

Question 8

CpG Islands

Answer 8

Located near promoter sequences adjacent to genes

Question 9

Histone Modification

Answer 9

• Chromatin is composed of DNA wound around an octamer of histone proteins to form nucleosomes
• Modifications occurs at conserved amino acid sequences in the N-terminal histone tails
• Chemical modification of histones alters the structure of chromatin, making genes accessible or inaccessible for transcription

Question 10

Acetylation by Histone Acetyltransferase (HAT)

Answer 10

Opens up the chromatin structure, making genes available for transcription

Question 11

Removal of the Acetyl groups by Histone Deacetylase (HDAC)

Answer 11

Closes the configuration, silencing genes by making them unavailable

Question 12

Histone Code

Answer 12

Sum of the complex patterns and interaction of histone modifications that change chromatin organization and gene expression

Question 13

RNA Interference

Answer 13

After transcription miRNA molecules associate with protein complexes to form RNA-induced silencing complexes (RISCs)

Question 14

Long noncoding RNA (lncRNA)

Answer 14

• Share many properties with mRNAs (5’ caps, 3- poly-A tails, splicing)
• Found in nucleus and cytoplasm of cells
• lncRNAs lack frame that codes for the insertion of amino acids into a polypeptide
• Binds to chromatin-modifying enzymes

Question 15

Imprinting

Answer 15

• Imprinted genes show expression of only the maternal allele or the paternal allele
• Parent-specific pattern of allele expression happens occurs during gamete formation

Question 16

Once a gene has been methylated and imprinted:

Answer 16

• Remains transcriptionally silent during embryogenesis and development
• Most imprinted genes direct aspects of growth during prenatal development

Question 17

Reprogramming

Answer 17

Occurs in the parental germ line and in the developing embryo just before implantation

Question 18

Human disorders

Answer 18

Associated with imprinting have their origins during fetal growth and development

Question 19

Cancer

Answer 19

• Hypomethylation is a property of all cancers examined to date
• Complex diseases have some strong links to environmental factors (lung cancer)
• Now viewed as a disease that involves both epigenetic and genetic changes that lead to alterations in gene expression

Question 20

DNA Hypomethylation

Answer 20

Reverses the inactivation of genes, leading to unrestricted transcription of many gene sets including oncogenes

Question 21

Hypermethylated genes

Answer 21

Include those involved in DNA repair, differentiation, apoposis, and drug resistance

Question 22

Evidence that supports stem cell involvement in epigenetic changes

Answer 22

• Epigenetic changes can replace mutation in silencing individual tumour-suppressor genes or activating oncogenes
• Global hypomethylation may cause genome instability and the large-scale changes chracteristic of cancer
• Epigenetic modifications are more effective than mutations in transforming normal cells int malignant cells

Question 23

Epigenetic Therapy

Answer 23

Reactivation of genes that have been silenced by methylation or histone modification

Question 24

Environmental Agents

Answer 24

Nutrition, chemicals, and physical factors such as temperature can alter gene expression by affecting the epigenetic state of the genome

Question 25

NIH Roadmap Epogenomics Project

Answer 25

Many aspects of health and susceptibility to diseases are related to epigenetic regulation or misregulation of gene activity

Question 26

Human Epigenome Project

Answer 26

• Collects and catalogs data on a set of human epigenomes to serve as reference standards
• Multinational, public/private consortium established to identify , map and establish the functional significance of all DNA methylation patterns in the human genome