Lecture 12

Question 1

posttranscriptional factors

Answer 1

plays an equal, if not more significant, role compared to transcriptional control

Question 2

mechanisms of posttranscriptional gene regulation

Answer 2

• control of alternative splicing
• mRNA stability
• translation
• RNA silencing

Question 3

alternative splicing

Answer 3

• generates different forms of mRNA from identical pre-mRNA
• expression of one gene gives rise to numerous proteins with similar and different functions
• increases the number of proteins made from one gene called isoforms

Question 4

casette exons

Answer 4

3 exons with 2 introns between them

Question 5

alternative 5’ or 3’ splice sites

Answer 5

4 exons with 2 introns between them, leaving the second and third exon together

Question 6

intron retention

Answer 6

3 exons with 2 introns between them

Question 7

mutually exclusive exons

Answer 7

4 exons with 3 introns between them

Question 8

alternative promoters

Answer 8

3 exons with 2 introns between them

Question 9

alternative polyadenylation

Answer 9

3 exons with 2 introns between them

Question 10

steady-state level of mRNA

Answer 10

• amount of mRNA in cell available for translation

- determined by combination of transcription and mRNA degradation rates

Question 11

half-life

Answer 11

• mRNA s degraded at some point after synthesis
• lifetime of mRNA varies
• regulated by cell needs

Question 12

what are the pathways of degradation?

Answer 12

• exoribonuclease enzymes: shorten length of poly-A called deadenylation dependent decay
• decapping enzymes: removes 7-methylguanine cap mRNA now unstable
• endonuclease cleaves mRNA internally

Question 13

phosphorylation

Answer 13

the most common type of posttranslational modification

Question 14

kinases

Answer 14

catalyze the addition of a phosphate group to ser, tyr, and thr amino acid side chains

Question 15

phosphatases

Answer 15

-enzymes that remove phosphate

Question 16

epigenetic trait

Answer 16

-a stable, mitotically and meitocally heritable phenotype that results from changes in gene expression without alterations in the DNA sequence

Question 17

epigenetics

Answer 17

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

Question 18

epigenome

Answer 18

-refers to the epigenetic state of a cell

Question 19

what has epigenetic been implicated in?

Answer 19

• progressive restriction of gene expression during development
• allele-specific expression in gene imprinting
• environment genome interactions during interactions during prenatal development that affect adult phenotypes
• human genetic disorders
• the loss or alteration of other epigenetic states can result in cancer

Question 20

epigenetic process

Answer 20

• stably alter gene expression patter and/or transmits the alteration at cell division
• includes cytosine methylation
• post-transcriptional modification of histone proteins and remodeling of chromatin
• RNA based mechanisms

Question 21

methylation

Answer 21

• reversible, addition of methyl groups

- epigenetic changes

Question 22

histone modification and chromatin remodeling

Answer 22

• alter the accessibility of genes for transcription

- epigenetic changes

Question 23

methylation

Answer 23

-occurs on cytosine bases adjacent to guanine called CpG dinucleotides, which are clustered in regions called CpG islands

Question 24

CpG islands

Answer 24

• located in and near promoter sequences adjacent to genes
• adjacent to essential genes are unmethylated and available for transcription
• other genes are methylated and transcriptionally silenced

Question 25

heterochromatic methylation

Answer 25

-maintains chromosome stability by preventing translocations and other chromosomal abnormalities

Question 26

histone modification

Answer 26

-important epigenetic mechanism of gene regulation

Question 27

what is chromatin composed of?

Answer 27

-DNA wound around an octamer of histone proteins to form nucleosomes

Question 28

where do histone modification occur?

Answer 28

-conserved amino acid sequences in the N-terminal histone tails, which protrude from the nucleosome

Question 29

what do chemical modifications of histones do?

Answer 29

-alter the structure of chromatin, making genes accessible or inaccessible for transcription

Question 30

how can amino acids in the N-terminal region of region of histones?

Answer 30

-modified by acetylation, methylation, and phosphorylation

Question 31

acetylation by histone

Answer 31

- acetyltransferase opens up the chromatin structure | - makes genes available for transcription

Question 32

removal of acetyl groups

Answer 32

- by histone deacetylase closes the configuration | - silences genes by making them unavailable

Question 33

histone code

Answer 33

the sum of the complex patterns and interactions of histone modifications that change chromatin organization and gene expression

Question 34

monoallelic expression (MAE)

Answer 34

only one allele is transcribed, while the other allele is transcriptionally silent

Question 35

what are the three major classes of MAE

Answer 35

1. parent of origin monoallelic expression: imprinting 2. random monoallelic expression: inactivation of the X chromosome 3. random monoallelic expression of autosomal genes

Question 36

what do imprinted genes show?

Answer 36

- parent of origin - the expression of only the maternal allele of the paternal allele - occurs during gamete formation

Question 37

what produces allele specific imprinting and subsequent gene splicing?

Answer 37

differential methylation of CpG rich regions

Question 38

what happens when a gene is methylated and imprinted?

Answer 38

it remains transcriptionally silent during embryogenesis and development

Question 39

what happens in the pattern of imprinting in mammals?

Answer 39

- it is reprogrammed every generation - when gamete formation begins in female/male germ cells, both chromosomes sets have their imprints erased and are each reprogrammed by changing the pattern of methylation to carry a female/male imprint that is transmitted to the next generation through the egg/sperm

Question 40

where does reprogramming occur?

Answer 40

in the parental germ line and in the developing embryo just before implantation -after implantation, differential genomic remethylation recalibrates which maternal and paternal alleles will be activated

Question 41

what do most implanted genes encode for?

Answer 41

growth factors or other growth-regulating genes

Question 42

where is the origin of most imprinted disorders?

Answer 42

during fetal growth and development

Question 43

BWS

Answer 43

- Beckwith-Weidemann Syndrome - disorder of imprinting - caused by abnormal patterns of DNA methylation resulting in altered patterns of gene expression

Question 44

random inactivation of an X chromosomes

Answer 44

- about half of embryonic cells randomly inactivate the maternal X chromosome and the other half inactivate the paternal X chromosome - silencing over 900 or so genes - once silenced it remains silent

Question 45

where are the 4 places that MAE genes can be throughout the genome

Answer 45

1. expression of both alleles (biallelic expression) 2. expression of only the maternal allele 3. expression of only the paternal allele 4. expression of neither allele

Question 46

what can alter gene expression?

Answer 46

- environmental agents including nutrition, chemicals, and physical factors such as temperature - affects the epigenetic state of the genome