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Genetics Exam 3 > Lecture 19 > Flashcards

Lecture 19 Flashcards

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1
Q

Eukaryotyic chromosomes are packed into

A

chromatin = DNA + histone proteins

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2
Q

chromatin compaction varies over cell cycle… _____
and along the length of the chromosome
based on ____

A

mitosis vs. interphase

transcriptional activity

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3
Q

Basic unit of the chromatin is the

A

nucleosome

complete nucleosome contains histone octamer, H1, and linker DNA

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4
Q

____ bp wraped around each octomer

A

146 bp

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5
Q

Histones ____ charged

A

basic, positively charged
>20% lys, arg

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6
Q

types of histones

A

5

H2A, H2B, H3, H4 - form octamer around which DNA is wrapped

linker histone: H1 - binds DNA that links adjacent nucleosomes (acts as tape - seals coilid DNA)

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7
Q

Histone H1 interactions can

A

condense chromatin further
(interact with each other - circle)

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8
Q

Heterochromatin

A

highly condensed chromatin

considered genetically ‘inert’
(gene poor, transcriptionally silent) - very little activity

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9
Q

Euchromatin

A

is more accessible (then heterochromatin)
- accessible to TFs

though not always transcriptionally active

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10
Q

Chromatin architecture(accessibility to enhancers, promoters) correlates with

A

transcriptional activity

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11
Q

Chromatin is maximally accessible at

A

transcriptional start sites (TSS)

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12
Q

epi” from the Greek:

epigenetic ___

A

upon, on, over
changes arise from chromatin conformation, not DNA sequence

regulation due to changes above level of DNA sequence

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13
Q

Chromatin architecture is controlled by several mechanisms including

A

replacement of histones with histone variants

“remodeling” of nucleosomes
→ movement of nucleosomes along DNA

covalent modification of histones (“marks”)
→ post-translational modifications to histone “tails” in nucleosome

DNA methylation

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14
Q

Histone marks are

A

post-translational modifications of histone tails

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15
Q

post-translational modifications of histone tails ocour by

A

addition/removal of acetyl, methyl, other groups (diferent functional groups)
mainly at H3, H4 (core)

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16
Q

Nomenclature of “histone code”

ex. H3K9Me1

A

H3K9Me1
H3 - Histone 3
K9 - amino acid residue - lysine 9
Me1 - modification - add methyl group

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17
Q

Histone marks control gene expression in two ways

A

1) electrostatic DNA-histone and histone-histone interactions destabilize or condense chromatin

2) modified tails serve as binding sites for proteins

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18
Q

Acytalation modifications (modified tails) are set or removed by

A

chromatin modifying enzymes

HDAC: histone deacetylase
HAT: histone acetyltransferase

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19
Q

HAT

A

histone acetyltransferase - neutralizes pos. charge of K; loosens association with negatively charged DNA

lysince has pos charge - interacts with DNA (-) to condence - add acytl group - nutralizes pos charge so + and - interaction occours with less strength

Acetylation “opens”

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20
Q

HDAC

A

histone deacetylase

Deacetylation condenses

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21
Q

Acetylated histones are enriched at

A

transcriptional start sites

ac- actelation - high at start site

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22
Q

Glucose overrides induction by galactose in

A

yeast GAL system

23
Q

In presence of glucose, the Gal system is repressed despite the presence of GAL4, due to

A

an epigenetic modification of histones

deacetylation by Tup1-Mig1 complex - binds more tightly

24
Q

Histones are methylated by ___

up to ___ _____ groups can be added

Effect is ____

A

histone methyltransferases (HMTase)

3 methyl

variable; depends on which residues are modified

25
Q

Histone methylation effect in transcription

A

variable

H3K4me3 is enriched near TSS

H3K4me1 is less near TSS

26
Q

DNA methylation usually _____ promoters

A

silences

(reminder - NOT histone methylation)

27
Q

DNA methylation often occurs on

A

cytosine nucleotides that are immediately adjacent to guanine nucleotides

referred to as CpG dinucleotides

(where p represents the phosphate group that connects the C and G nucleotides)

28
Q

DNA methyltransferase recognizes

A

CpG dinucleotides

CpG = side-by-side, 5’-CpG-3’(as opposed to base-paired)

adds methyl group (CH3) to cytosine base - making 5-methylcytosine

29
Q

another enzyme called ____ convert 5-methylcytosine back to cytosine

A

demethylases

30
Q

the methylation pattern of DNA is maintained across cell division BY

A

Immediately after semiconservative replication, the cytosine base on the template strand is methylated, but the cytosine base on the newly replicated strand is unmethylated.

Methyltransferase enzymes recognize the hemimethylated state of CpG dinucleotides and add methyl groups to the unmethylated cytosine bases,

resulting in two new DNA molecules that are fully methylated.

31
Q

In mammals,_____CpGs methylated genome-wide

Exception in CpG of _____

A

> 70%

active promoters - Normally protected from methylation

32
Q

In cancer cells, there are aberrant DNA methylation patterns

at ____ and ____

A

at promoters (effect is local)
at insulators (and other regulatory elements) with larger scale consequences

33
Q

Aberrant DNA methylation can dysregulate gene expression on

A

larger scales

CTCF binding is methylation sensitive

Loss of binding through methylation allows aberrant enhancer-gene interactions

34
Q

3 examples of epigenetic gene silencing as part of normal organismal development

A

1) Reproductive versus worker casts in honeybees
2) X chromosome inactivation
3) Genomic imprinting

35
Q

____ controls reproductive status in honeybees

A

DNA methylation

queen and woker - identical genetic material

Royal jelly - fed only to queen bees - blocks methylation (silencing expresson of Dnmt3 - normally adds methyl groups)

DNA methylation is responsible for worker phenotype

36
Q

DNA methylation suppress gene expression by

A

1) presence of the methyl group in the major groove inhibits the binding of transcription factors and other proteins required for transcription to occur.

2) 5-methylcytosine also attracts certain proteins that directly repress transcription

3) DNA methylation attracts histone deacetylase enzymes, which remove acetyl groups from the tails of histone proteins, altering chromatin structure in a way that represses transcription (s

37
Q

recise and widely used technique for analyzing DNA methylation is

A

bisulfite sequencing

38
Q

Female-specific epigenetic silencing of the X chromosome lasts ___

Inactivation established by ____

A

a lifetime

Mechanism of dosage compensation (shits down/inactivates one copy) involving DNA and histone methylation

Inactivation established by large noncoding RNA - transcript exists - recruits factors - methylate - inactivation

(XIST: X-inactivation-specific transcript
specified by the X-inactivation center (XIC) on the X to be inactivated)

39
Q

Genomic imprinting is ___

Durring imprinting ____

A

gender-specific gene silencing

maternal/paternal alleles differentially marked by DNA methylation (of IC, imprinting center) during gametogenesis

results in mono-allelic parent-of-origin-specific expression of subset of genes

40
Q

Majority of genes in mammals display Mendelian pattern of expression

A

normal alleles inherited from each parent are expressed equally
<1% of genes are imprinted

41
Q

dosage compensation

A

shits down/inactivates one copy

Mechanism involves DNA and histone methylation

42
Q

Differentially imprinted genes tend to be

A

clustered

43
Q

Differential imprinting is controlled by

A

DNA methylation of the IC during gametogenesis

44
Q

Prader-Willi Syndrome (PWS) results from

A

loss of expression from paternal-only expressed genes on chr 15

Loss of expression most commonly caused by interstitial deletions of chr 15

Characterized by infantile feeding problems, hyperphagia, developmental delay, intellectual disability, behavioral problems

45
Q

Angelman Syndrome (AS) results from

A

loss of expression from maternal-only expressed genes on chr 15

Loss of expression most commonly caused by interstitial deletions of chr 15

Characterized by infantile feeding problems, hyperphagia, developmental delay, intellectual disability, behavioral problems

46
Q

PWS and AS suggests that

A

we need both copies of this region

47
Q

epigenetic markers

A

histone modifications, as well as changes to DNA that do not involve the base sequence, have been shown to be associated with the level of transcription

48
Q

Crosstalk between epigenetic markers occurs because

A

histone modifications attract enzymes and proteins that modify other histones.

49
Q

paramutation

A

an interaction between two alleles that leads to a heritable change in the expression of one of the alleles

Some epialleles may undergo paramutation, a trans-interaction between alleles that induce heritable expression change in one allele.

fetures
- tramited even when the allele that brought about the alteration is no longer present.
- altered allele is now able to convert other alleles to the new phenotype
- no associated DNA sequence changes in the altered alleles

50
Q

epialleles

A

Alleles that do not differ in their base sequence but have epigenetic differences that produce heritable variations in phenotypes.

Some epialleles may undergo paramutation, a trans-interaction between alleles that induce heritable expression change in one allele.

51
Q

X-inactivation center

A

a particular segment of the X chromosome that controls the particular X chromosome inactivated within a cell

key player in X inactivation is a gene called Xist (for X-inactive specific transcript), which encodes a long noncoding RNA (lncRNA)

however Several genes within the X-inactivation center interact to bring about the inactivation of one X chromosome while keeping the other X chromosome active.

52
Q

Beckwith-Wiedemann syndrome

A

small deletions on chromosome 11 that interfere with the normal process of imprinting

53
Q

possible explanation for genomic imprinting is the

A

genetic conflict hypothesis

suggests that there are different and conflicting evolutionary pressures acting on maternal and paternal alleles for genes (such as Igf2) that affect fetal growth.

Genetics Exam 3 (8 decks)

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