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CBFM - M1T1 > Epigenetics & Transcription Regulation > Flashcards

Epigenetics & Transcription Regulation Flashcards

1
Q

Which methyltransferases are responsible for de novo DNA methylation?

A

DNMT3a & DNMT3b

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2
Q

What is the function of histone acetyl transferases (HATs)?

A

HATs add an acetyl group to histone tails. Acetylation is associated with euchromatin formation and active transcription.

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3
Q

What is epigenetic drift?

A

Gradual hypomethylation with aging. This is likely random due to imperfect maintenance. The rate of drift is influenced by environmental factors.

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4
Q

What term describes the heritability of epigenetic signals?

A

Mitotic heritability

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5
Q

What is the relationship between methylation and cancer?

A

Hypomethylation may lead to increased recombination, gene arrangements, and genomic instability.

Hypermethylation of CpG islands in promoters may lead to decreased expression of tumor suppressor and DNA repair proteins.

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6
Q

What is the importance of epigenetic signals in cellular function?

A

They play a role in cell differentiation and maintenance of that differentiated state.

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7
Q

What steps are taken to “reprogram” DNA methylation during gametogenesis?

A
  1. Global demethylation and reactivate the inactive X chromosome
  2. Imprints are established (paternal = sperm, mother = egg)
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8
Q

When is most DNA methylation established?

A

During development in utero

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9
Q

What general factors influence transcription?

A

Internal & external factors

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10
Q

What are the causes of imprinting disorders?

A
  1. Mutation or deletion of the active allele
  2. Failure to imprint or loss of imprinting
  3. Uniparental disomy
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11
Q

What enzyme adds an acetyl group to histone?

A

Histone acetyl transferases (HATs)

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12
Q

What process is associated with gene inactivation and inhibition of transcription?

A

Methylation

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13
Q

What molecule is used to methylate both DNA and histones?

A

s-adenosyl methionine (SAM)

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14
Q

What is the relationship between transcription rate and protein production?

A

The greater the rate of transcription, the more protein the is produced from that gene.

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15
Q

What is the most common DNA mutation in humans?

A

Methylated cytosine to thymine

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16
Q

What is uniparental disomy?

A

A mistake during the segregation of chromosomes in meiosis that results in the formation of an egg or sperm with 2 copies of a chromosome. If both copies remain after fertilization, this results in uniparental disomy. This may or may not result in phenotypic differences in normal (non-imprinted) genes.

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17
Q

What are the two general methods in which transcription may be regulated?

A
  1. Regulation of TSFs.
  2. Regulation of chromatin through epigenetic signals.
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18
Q

What molecule provides acetyl groups for histone acetylation?

A

acetyl-CoA

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19
Q

How are histones distributed during somatic cell division?

A

Parental histones are distributed evenly between both daughter cells. As a result, only half of all daughter histones are appropriately modified with epigenetic signals.

20
Q

What steps, if any, are taken to “reprogram” DNA methylation during embryonic development?

A
  1. Global demethylation - with the exception of imprinted genes
  2. X chromosome inactivation in female embryo
  3. De Novo methylation during cell differentiation
21
Q

Describe the process of lyonization (silencing of the X chromosome).

A

Both chromosomes carry the XIST gene, which transcribes into long non-coding RNA. The lncRNA coats the inactivated X chromosome and recruits complexes for histone modification.

22
Q

CpG sequences are underrepresented in the genome, likely as a result of mutation of methylated cytosines to thymine. Why then do islands of CpG remain in regulatory regions of many housekeeping genes?

A

Actively transcribed genes are not methylated. Since cytosine in these CpG island regions was not methylated, mutation was much less likely thus maintaining the sequence.

23
Q

What dietary substances are needed to produce s-adenosyl methionine (SAM)?

A

Folate & B Vitamins

24
Q

What does it mean to say that transcription is under combinatorial control?

A

Most genes are under the control of multiple TSFs, which may be activated by multiple signaling pathways. The probability of transcription is determined by the net effect of all these TSFs.

25
Q

What is the role of DNMT1?

A

Called the maintenance methylase, it is responsible for maintaining established methylation patterns during DNA replication. DNMT1 acts similarly to reader-writer complexes.

26
Q

What enzymes add methyl groups to CpG sequences?

A

DNA methyltransferases (DNMTs)

27
Q

What term describes the modification of phenotypes in utero through epigenetic patterns so that offspring are better adapted for the environment they will be born into?

A

Developmental plasticity

28
Q

In what ways is DNA methylation and gene inactivation beneficial?

A

X chromosome inactivation, imprinting, cell differentiation, chromosomal stability

29
Q

What disorder results from the deletion of paternal chromosome 15?

A

Prader-Willi Syndrome

30
Q

In what cell type are epigenetic signals inherited?

A

Somatic cells only. Epigenetic signals are erased from germ cells before meiosis.

31
Q

What reaction commonly activates TSFs?

A

Phosphorylation

32
Q

What is the relationship between DNA methylation and chromatin structure?

A

Methylation correlates with deacetylation of histones and formation of heterochromatin.

33
Q

What is a Barr body?

A

Dense chromatin of the inactivated X chromosome

34
Q

What is a histone?

A

A small, positively charged protein to which DNA winds and forms a nucleosome.

35
Q

Where is acetyl CoA for acetylation acquired?

A

From the metabolism of carbohydrates and fatty acids

36
Q

What term describes chromatin that sometimes exists as euchromatin and other times as heterochromatin?

A

Faculative

37
Q

What effect does the microbiome have on epigenetics?

A

Some bacteria produce substances that inhibit HDACs, which would then promote transcription.

38
Q

Which X chromosome is silenced in X chromosome inactivation?

A

The silenced X chromosome is randomly selected by the cell. However, different cells may silence different X chromosomes. Some genes at the tip of the short arm of the silenced chromosome may still be expressed as homologous genes are present on the Y chromosome.

39
Q

What is genomic imprinting?

A

Imprinting refers to the permanent inactivation of one allele in all cells, specific for the parent from which the allele came.

40
Q

What enzymes function to re-establish parental histone modification on newly synthesized daughter histones?

A

Reader-writer remodeling complexes. They bind the parental histone, read modifications, and write those modifications on the daughter histone.

41
Q

What is the purpose of X chromosome inactivation?

A

Dosage compensation - ensures that females produce X-linked gene products in amounts similar to males

42
Q

What enzyme removes DNA methylation via oxidation?

A

TETs

43
Q

What is the function of genomic imprinting?

A

To adjust gene dosage. Genomic imprinting is based on the Conflict Theory, which states competing interests of the mother and father result in silencing of some alleles in a parent-specific manner.

44
Q

How do epigenetic signals influence gene expression?

A

Signals influence chromatin structure, thus regulating DNA accessibility to TSFs. Epigenetic signals do NOT change DNA sequences or genes.

45
Q

What enzyme removes an acetyl group from histones?

A

Histone deacteylase (HDAC)

46
Q

What disorder is the result of the deletion of the maternal chromosome 15?

A

Angelman Syndrome

47
Q

In what cells are TETs most commonly found?

A

Most abundant in germ cells and embryonic stem cells as previous epigenetic signals are removed. TETs are present in low levels in somatic cells to prevent methylation of certain regions.

CBFM - M1T1 (42 decks)

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