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Human Molecular B > Lecture 3 - Regulation Of Chromatin Structure > Flashcards

Lecture 3 - Regulation Of Chromatin Structure Flashcards

1
Q

What are centromeres characterised by?

A

Specific histone H3 variant (CenpA or CenH3)?

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2
Q

What do centromeres in higher eukaryotic chromosomes contain in large amounts?

A

Repetitive DNA and unique histone variants

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3
Q

What type of structure does a centromere have?

A

Heterochromatin

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4
Q

What is the structure of heterochromatin like?

A

The structure is inaccessible and repressive No Replication No Transcription No DNA repair

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5
Q

What is the structure of Euchromatin like?

A

The structure is accessible and extended Replication Transcription DNA repair

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6
Q

What is chromatin remodelling?

A

The energy-dependent displacement of reorganisation of nucleosomes that occurs in conjugation with activation of genes for transcription There are numerous ATP-dependent chromatin remodelling dimpled that use energy provided by hydrolysis of ATP

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7
Q

What can remodelling complexes do?

A

Alter, slide or displace nucleosomes

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8
Q

What are histone post translational modification?

A

Covalent in nature Lysine methylation Lysine acetylation Lysine ubiquitilation Lysine sumolyation
Arginine methylation Glutamate ADP ribosylation Threonine phosphorylation.
Serine phosphorylation Tyrosine phosphorylation Arginine deimination (citrullination)

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9
Q

What is side chain modification?

A

Histone tails are highly conserved and are modified on specific amino acids Modification of amino acid side chains can alter structure/function

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10
Q

What is direct effect of side chain modification?

A

Change in charge

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11
Q

What is the indirect effect of side chain modification?

A

Change in charge

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12
Q

Histone modification

A

Histone modifications are mutually exclusive e.g. lysine cannot be methylated if already acetylated and vice versa Marks are reversible

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13
Q

What does chromatin modification function depends on?

A

Specific modification ‘reader’

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14
Q

Methylation

A

KMTs

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15
Q

Demethylation

A

KDMs

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16
Q

Acetylation

A

HDACs

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17
Q

De acetylation

A

HATs

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18
Q

Phosphorylation

A

Kinase

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19
Q

Dephosphorylation

A

Phosphatases

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20
Q

What is HAT?

A

Histone acetyltransferase

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21
Q

What is Lysine acetylation/deacetylation of histone tails?

A

Acetylation of Lysine residues in histone tails Loss of positive charge Reduction in binding to DNA Opening up of chromatin Access to DNA

22
Q

HDAC

A

Histone deacetylase

23
Q

What is TAFII250 bromodomain?

A

Acetylates Transcriptional activation

24
Q

Histone modifying complexes have several components

A

Histone modification enzymes have little, if any, specificity other than for Lysine, they have the ability to acetylation/deaceytlate ANY Lysine on ANY histone or nucleosome

25
Q

What is histone acetylation associated with?

A

Transcription activation

26
Q

What is Lysine (K) acetyltransferase (KAT) ?

A

An enzyme present in large complexes that acetylates Lysine residues in histones AKA histone acetyltransferase

27
Q

What is transcription activators associated with?

A

Histone acetylase activities in large complexes

28
Q

What is histone deacetylase (HDAC)?

A

Enzyme that removes acetyl groups from histones May be associated with repressors of transcription

29
Q

Where are deacetylase present ?

A

Complexes with repressor activity

30
Q

Where do distinct enzyme activities exist ?

A

Both methylation for and demethylating Lysines (mono, di, tri)

31
Q

What is context dependent?

A

Different methylated Lysine’s can recruit activators or repressors

32
Q

What is methylation catalysed by?

A

Histone methyltransferase (KMTs)

33
Q

What is demethylation catalysed by?

A

Histone demethyltransferase (KDMs)

34
Q

What is HP1 chromodomain?

A

Methylates Heterochromatin assembly Transcriptional silencing

35
Q

How can processes such as transcription be regulated?

A

By switching modifications

36
Q

What is DNA methylation?

A

Covalent addition of a methyl group onto 5th position of cytosine within self complementary CpG dinucleotides Catalysed by DNA methyltransferase

37
Q

What does DNA methyltransferase do ?

A

Flip bases out of the double helix

38
Q

What are examples of highly methylated sequences?

A

Satellite DNA Repetitive element (transposons and relic) Non-repetitive intergenic DNA and exons of genes

39
Q

What is the percentage of CpG in human somatic cells that are methylated (global methylation)?

A

70-80%

40
Q

Approximately how many CpG islands in human genome?

A

45,000

41
Q

Where are CpG islands present?

A

Nearly all constitutively active house keeping genes

42
Q

What are CpG islands in normal tissue?

A

Unmethylated

43
Q

What does DNA methylation do?

A

Compact chromatin and is associated with Transcriptional repression

44
Q

What are the 3 types of modification that affect chromatin?

A
  1. Acetyltransferase/deacetylase 2. Histone methyltransferase/demethylase 3. DNA demethylase/ DNA methyltransferase
45
Q

Acetyltransferase/deacetylase

A

Remodelling complexes can facilitate binding of acetyltransferase complexes

46
Q

Histone methyltransferase/demethylase

A

Histone methylation can also recruit chromatin-modifying complexes

47
Q

What do different modifications and complexes facilitate?

A

Transcription, initiation and elongation

48
Q

DNA demethylase/ DNA methyltransferase

A

DNA methylation and histone modification act in concert to regulate transcription in the chromatin environment

49
Q

What are modification?

A

Reversible and therefore dynamic

50
Q

Inactive to active state

A

Histone acetyltransferase Histone demethylase DNA demethylase

51
Q

Active to inactive state

A

Histone deacetylase Histone methyltransferase DNA methyltransferase

Human Molecular B (13 decks)

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