define epigenetics
the study of heritable modifications of chromatin (DNA or histones) that alter cell- and tissue-specific patterns of gene expression without changing the DNA sequence.
epigenome is the result of
epigenetic changes
function of epigenome
regulate normal development or generate physiological responses to environmental signals.
epigenetic modifications are reversible, true or false
true
can epigenetic changes be inherited
yes, they can be transmitted to daughter cells by MITOSIS and future generations by MEIOSIS
what are the 3 major epigenetic mechanisms?
DNA methylation, covalent modification of histone tails, the action of miRNAs
define DNA methylation
Addition of a methyl group (-CH3) to cytosines that are next to guanines
where is DNA methylation concentrated?
at "CpG islands" in/near gene promoters
DNA methylation is associated with which and processes and how?
gene silencing and decreased transcription
describe dosage compensation
in female mammals, the inactivated X chromosome is heavily methylated as part of the silencing mechanism
define imprinting
an epigenetic phenomenon by which certain genes can be expressed in a parent-of-origin-specific manner
with imprinting, differential methylation of CpG-rich regions and promoter sequences leads to
silencing of either the maternal or paternal allele of a gene
Imprinting is reset during
gamete formation in either parent
as a result of imprinting, chromosomes passed to offspring have different inactivated regions depending on
parent of origin
eukaryotic DNA is combined with what to form chromatin
histone and non-histone proteins
the compactness of chromatin inhibits which processes
transcription, replication, and DNA repair
The blank stick out from nucleosomes and can be blank modified
N-terminal tails of histones; covalently
how do modifications to histone tails increase or decrease expression of nearby genes
by directly altering the chromatin structure or by acting as signals to recruit other proteins (e.g. transcription factors).
name 4 different types of histone modifications
methylation, acetylation, ubiquitination, phosphorylation
the effect of some histone modifcations depends on what
which amino acid position is affected.
e.g. methylation of H3K4 (lysine 4 of histone H3) activates transcription while methylation of H3K9 represses it
describe histone acetylation
Acetylation of histone tails can alter the attraction between positively charged histones and negatively charged DNA
effects of histone acetylation
leads to a looser association between DNA and histones ("open" configuration) and increased transcription.
effects of histone deacetylation
opposite effect of acetylation (leads to "closed" configuration and decreased transcription).
define histone code
The sum of the complex patterns and interactions of histone modifications that change chromatin organization and gene expression
combinations of histone modifications allow
differentiated cells to carry out cell-specific patterns of gene transcription and respond to external signals that modify the patterns without any changes in DNA signal
3 categories of Regulatory proteins that act through histone modifications
writing (transcription), erasing, reading (translation)
which regulatory proteins fall under transcription-related histone modifications
acetylases, methylases, phosphorylases
which regulatory proteins fall under erasing-related histone modifications
deacetylases, demethylases, phosphatases
which regulatory proteins fall under translation-related histone modifications
bromodomain, chromodomain, PHD finger, WD40 repeat
describe chromatin remodeling
Repositioning or removal of nucleosomes to make promoter regions accessible or inaccessible to transcription factors.
3 forms of ATP-dependent chromatin remodeling
alteration of DNA-histone contacts; alteration of the DNA path; remodeling of nucleosome particle
result of alteration of DNA-histone contacts
sliding exposes DNA
result of alteration of DNA path
DNA pulled of nucleosome
result of remodeling of nucleosome particle
nucleosome dimer forms
describe role of miRNAs in epigenetics
RITS complexes convert euchromatic chromosome regions into facultative heterochromatin, which silences genes located within these newly created heterochromatic regions.
how are the effects of miRNAs in epigenetics reversible
can be converted to euchromatin, which is accessible for transcription.
genetic mutations have changes in their
epigenome
cancer cells have changes in their
epigenome
cancer cells vs normal cells in terms of epigenetics
Both histone modification patterns and DNA methylation differ in cancer cells compared to normal cells.
Mutations in the genes of blank are linked to the development of cancer
histone-modifying proteins such as histone acetyltransferase (HAT) and histone deacetylase (HDAC)
less methylation = more or less expression?
more
the genome of cancer cells tends to be hypermethylated or hypomethylated
hypomethylated (less methylation=more expression)
hypomethylation allows the possibility of turning on
oncogenes (genes that promote cancer when overexpressed)
effect of hypermethylation at CpG islands and promoters
silences certain genes, including tumor-suppressor genes like those that control DNA repair, differentiation, and apoptosis
examples of environmental agents that can alter gene expressing by affecting the epigenetic state of the genome
nutrition, chemicals, and physical factors such as temperature
epigenetic changes caused by enironmental changes are heritable or inheritable?
heritable; e.g. A reduced protein diet fed to rats during pregnancy results in permanent changes in the expression of several genes in the F1 and F2 offspring