Exam 5: Epigenetic Phenomena Flashcards Preview

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Flashcards in Exam 5: Epigenetic Phenomena Deck (32):


DNA methyltransferase (DNMT) inhibitor that causes hypomethylation of the genome
potential to counteract malignancies associated with hypermethylation
therapy for acute myeloid leukemia


Angelman syndrome (AS)

caused by deletion on maternal chromosome 15
unusual facial features, seizures, movement and gait disorders, severe mental retardation
(parent of origin effect)


Beckwith-Wiedemann Syndrome (BWS)

uniparental disomy
child inherits both homologues of a portion of chromsome 11 from father
overabundance of insulin-like growth factor 2 - leads to kidney, adrenal, and liver problems resulting in severe hypoglycemia
susceptibility to childhood cancer


Boundary elements

chromatin barriers
separates active and inactive genomic regions - stops spread of inactivation region caused by cytosine methylation self-propagation


chromatin barriers

boundary elements
stop spread of inactivated region of DNA (caused by cytosine methylation) and separates active and inactive genomic regions


CpG islands

clusters of CpG dinucleotide repeats close to 5' region of genes
generally unmethylated
CpG dinucleotide repeats are very susceptible to methylation - methylation of CpG islands shut down expression of neighboring genes


CpG dinucleotide repeat

very susceptible to methylation on cytosine residues - silences chromosomal region
about 70% in human genome are silenced by methylation - includes highly repetitive DNA, telomeres, and centromeres


de-novo DNA methylation

methylation of unmethylated cytosine bases of DNA
introduced into unmethylated strand of DNA by DNA methyltransferases DNMT3a and b


DNA methyltransferase (DNMT) inhibitors

inhibitor that causes hypomethylation of genome - counteracts malignancies associated with hypermethylation
therapy for acute myeloid leukemia


DNA methyltransferase DNMT1

maintains pattern of DNA methylation throughout mitosis
during DNA replication, non-methylated strand is synthesized on methylated template strand
non-methylated strand is methylated by DNMT1



study of stable, heritable changes in gene expression that do not involve changes in DNA sequence
important for: imprinting during development & gametogenesis, inactivation of X-chromosome, and progression of cancer


genomic instability

can be caused by hypomethylation (de-methylation of silent chromatin) - initiating transformation of a cell into a tumor cell
leads to somatic recombination - Non-homologous recombination
leads to drastic increase in mutations in established tumor


histone acetyltransferases (HATs)

acetylates histones, decreasing their binding affinity to DNA and facilitates transcription
Histone modification


histone de-acetylase (HDAC) inhibitors

promote histone hyperacetylation and gene re-expression in chronic lymphocytic leukemia



lead to expression of genes in normally silent regions of genome
leads to re-expression of silenced genes and expression of endogenous retroviruses
reactivate transposable elements - leads to somatic recombination and genomic instability


histone deacetylases (HDACs)

remove acetyl groups from histones
favors binding of histones to DNA (increases binding affinity), leading to chromatin condensation & silencing of transcription


histone methylases

bind to HP1 proteins that are bound to methylated histones (after de-acetylation of histones)
methylation of histones spread long chromosomes until a boundary element is reached
methylases allow chromatin inactivation to spread


HP1 proteins

bind to methylated histones after histones have been de-acetylated
bind histone methylases to spread chromatin inactivation



shuts down expression of genes close to CpG islands
silences gene transcription
may cause cancer by silencing tumor suppressor genes


maintenance of DNA methylation

maintained through mitosis by DNA methyltransferase DNMT1 by methylating non-methylated strand after DNA replication


methylcytosine binding proteins (MBPs)

binding brings about repression of transcription
occurs after a stretch of DNA has been methylated by DNA methyltransferases
interact with repressors of transcription (blocks transcription of nearby genes) & histone deacetylases (HDACs) (remove acetyl groups from histones leading to chromatin condensation/inactivation of transcription)


parent of origin effect

inheritance of genetic variation from the mother or father
certain genes expressed due to imprinting - phenotypic variation


Prader-Willi syndrome (PWS)

deletion on paternal chromosome 15
characterized by obesity, excessive food seeking behavior, hypogonadism and mental retardation
(parent of origin effect)


retrotransposons in human genome

transcriptionally inactive DNA
mobile genetic elements that could cause mutations/disease if not silenced by methylation
about 45% of human genome derived from retrotransposons of viral origin
silenced by methylation


uniparental disomy

abnormality where rescue of an aneuploid zygote where surplus chromosome is lost & rescued zygote retains both chromosomes from same parent
can lead to a situation in which an individual has only maternally or only paternally imprinted homologues of a chromosome
Can lead to problems with gene dosage - overabundance on one gene and lack of another


X-chromosome inactivating center (XIC)

contains XIST (inactive X-specific transcript) gene - gets transcribed on X-chromosome to be inactivated
inactivation of X-chromosome proceeds via imprinting


XIST (inactive X-specific transcript)

in XIC of X-chromosome, gene transcribed on X-chromosome to be inactivated
RNA associates closely with X-chromosome and mediates inactivation of most of the chromsome
DNA and histones on X chromosome to be inactivated are methylated - shuts down expression of most genes



tightly packed DNA - histones are deacetylated & methylated, DNA methylated - transcription silenced



loosely packed DNA - histones acetylated, DNA not methylated - transcriptionally active



form of DNA silencing, shuts down certain chromosome regions & maintained throughout mitosis
marks chromosome as having come from father or mother - some genes are repressed of maternal chromosome while others of paternal
takes place during gametogenesis - imprinting center (silences chromosomal regions by DNA methylation and histone deacetylation)


Imprinting important in 2 biological processes:

Development - cell type specific imprint established
Maturation of gametes - gametogenesis, parent of origin specific imprint imposed on chromosomes (make all inherited chromosomes look either maternal or paternal)


Cancer can result from hypo or hypermethylation by:

hypomethylation - demethylation (& overexpression) of oncogenes, expression of silent chromatin - somatic recombination, increase in mutations
hypermethylation - silencing of tumor suppressor genes