Epigenetics Flashcards
6 steps to control eukaryotic gene expression:
transcriptional control, RNA processing, RNA transport, translational control, mRNA degradation, and protein processing
Most Epigenetics takes place during ____ control
Transcription
_____ is heritable changes in gene expression that don’t involve changes to the underlined DNA sequence. Change in phenotype without change in genotype
Epi-genetics
Epigenetic change is a ___ and ____ occurrence but epigenetic change is influenced by factors like age, environment, and disease state
Regular and natural
Normal functions of epigenetics include:
Cell differentiation, maintenance of genome structure, suppression of repetitive elements in invasive DNA, dosage compensation between XY and XX, and genomic imprinting
______ is a set chemical modifications to DNA and DNA associated proteins which alter gene expression and are heritable via meiosis and mitosis.
Epi-genome
DNA methylation and histone modification are common ____ of Epigenetics
Mechanisms
Euchromatin is associated with ____ DNA versus heterochromatin is associated with _____ DNA
Unmethylated
Methylated
The DNA _____ state is inherited
Methylation
_____ at histones promotes Euchromatin
_____ at histones promotes heterochromatin
Acetylation
Phosphorylation
When a methyl group is added to a ____ in DNA, this promotes heterochromatin and gene silencing
Cytosine
_____ ____ are CpG sequences 200 to 1000 base pairs.
_____ CpG islands are in/near promoters of active genes 60 to 70% of promoters have CPG islands.
_____ CpG islands are within large repetitive sequences and in intergenic regions they are next to genes that are silenced in a specific tissue
CpG islands
Unmethylated
Methylated
Cytosines are methylated by ___ ____ at the five carbon. _____ is a type of DNA methyl transferees that maintains existing methylation patterns following DNA replication. _____ and ____ target previously unmethylated CpGs they are highly expressed in the embryo during implantation and establish new methylation patterns
DNA methyltransferases
DNMT1
DNMT3A and DNMT3B
CpG represents a _____ DNA sequence when it is double stranded making it easy for it to be recognized and inherited
Palindromic
_____ _____ is when new DNA strands are not methylated during DNA replication, the methylated DNA gets diluted out as the cell or embryo goes through multiple cell divisions
Passive demethylation
____ ____ is by so-called TET (ten-eleven translocation) enzymes
Active demethylation
____ is a process by which some genes are epigenetically silenced during game to genesis in a parent of origin specific manner, which results in only one ____ being expressed for the imprinted loci
Imprinting
Allele
The main mechanism of epigenetic imprinting is ____ ____
CpG methylation
The fertilized ovum is ____ meaning it has the potential to become an entire organism and to make the placenta tissue
Totipotent
Epigenetic modifications during development determines ___ ____ and feet by limiting the developmental potential of individual cells and their progeny
Cell differentiation
The zygote must have many prior epigenetic marks ____ because both the eggs and Sperm had genomes of specialized cells: ____ and ___
Now we have to be able to make all cell types
Erased
Spermatozoa and oocytes
Zygote genome has both male and female imprinted marks from paternal and maternal chromosomes, marks need to be erased so that ____ ___ of gametes based on its own genotypes can be expressed. It also needs to be _____ silent
Sexual determination
Transposons
Epigenetic reprogramming occurs at two different points during development:
1. In the ____ before the blastocyst stage
2. In the ____ ___ ____ within the developing embryo
Zygote
Primordial germ cells (PGCs)
In the zygote, the maternal and paternal genomes undergo ___ ____ resetting the genome for totipotency (ability to make all cell types) at the ____ stage.
Global demethylation
Blastocyst
There is another round of global demethylation during migration of the ____ ____ ___. It’s thought that most imprinted alleles are not erased so that there are parent specific ____ patterns
Primordial germ cells
Methylation
Need to be able to equalize the gene expression in individuals with 2X compared to those with one X. Change the gene _____ by _______. The X gets condensed down into a ____ ____. This is called _____
Regulation
X inactivation
Barr body
Lyonization
X inactivation is initiated by a ___ _____ ___ called Xist. Xist is transcribed from the __ ______ ____ of the chromosome to be silenced. Xist coats Xi and serves as a scaffold for modifying enzymes.
Long non-coding RNA (lncRNA)
X inactivation center (XIC)
Xi displays _____ histone modifications and DNA methylation
Xa displays _____ modifications
Somehow, XIC senses the number of X chromosomes and ____ silenced one
Repressive
Activating
Randomly
_____: heritable change in gene activity not associated with a DNA sequence change. Results from _____ changes, or defects in epigenetic control mechanisms that cause deregulation
Epimutation
aberrant
Epimutations affect many aspects of human health including ____ and ___ health
Metabolism
Mental
Epimutations can drive carcinogenesis, 20% of sporadic breast cancers display ____ of the BRCA1 promoter
Hypermethylation
Epigenetic deregulation on a molecular level:
Epigenetic inheritance:
Week 3 of gestation, primordial germ cells are already forming, thus the babies future gametes can be _____ exposed to an epigenetic event
Directly
_____ _____: transmission of an induced trait from one generation to another without direct exposure
Transgenerational inheritance
______ _____= prenatal exposure: the mom (F0) is exposed while she is pregnant. The child’s (F1) somatic cell epigenome is programmed by the exposure but not it’s germline. The grandchild (F2) are unaffected. Direct exposure of the F1 child
Intergenerational inheritance
_______ _____: the child (F1) is exposed during gestation and so are the child’s developing germ cells (F2). The grandchild (F2) will have a phenotype but does not pass it to his/her own children (F3) because those gametes are reprogrammed back to normal during development. Direct exposure of the F2 child
Multigenerational inheritance
______ _____: the F1 gametes are modified during gestation so the F2 child is affected. If these marks are not erased during PGC differentiation, F2 gametes remain affected and the F3 generation has the altered phenotype. Indirect exposure
Transgenerational inheritance
The evolution of metabolic epigenetic marking is thought to enhance ____ ____ by programming energy balance so that available nutrients are used most efficiently
Offspring survival
Metabolic epigenetic marking allows for quicker adaptation to the environment than ____
Evolution
Metabolic epigenetic marking is the programming of an offspring’s future metabolic responses by a stimulus that occurs during ____ ____ ____
Critical embryological periods
Example of metabolic epigenetics is maternal diet of mice can affect the ____ of the offspring. It takes 3 generations of a normal maternal diet to reverse these changes
Length
Women who were pregnant in the Dutch hunger winter famine only ate 400 to 800 calories per day and delivered low ___ ____ babies. By 50, those offspring had increase BMI, schizophrenia, diabetes. Likely caused by the _____ of the ____ locus compared to their same sex siblings
Birth weight
Hypomethylation
IGF2
Both ____ and _____ of the mother can lead to obese phenotypes
Overnutrition and undernutrition
____ ____ ____ is associated with insulin resistance in young adults
Prenatal psychosocial stress
____ ____ ____ is associated with offspring having several metabolic syndrome conditions
Maternal holocaust exposure
____ ____ during the preconception or prenatal period: offspring at increase risk for developing type II diabetes
Maternal bereavement
Hypermethylation of tumor suppressor genes can cause ____. Global genomic ____ where all genes are expressed can lead to cancer. Persistence of ___ ___ inappropriately can lead to cancer
Cancer
Hypomethylation
m5c Residues
Cancer:
____ increase and methylate CpG islands in tumor suppressor genes. It is proposed that ____ decrease and repetitive elements and oncogenes become demethylated
DNMTs
DNMTs
Many ________ and _____ syndromes are caused by altered or defective function of epigenetic machinery: ability to read, write, erase, and remodel markings. Misregulation of ___ and ____ ____ are common features of disorders
Neurodevelopment
Developmental
Growth
Intellectual disability
Imprinting disorders:
Beckwith wiedemann syndrome is an ___ disorder, only paternal imprinting present
Silver Russell syndrome is an ___ disorder only maternal imprinting present
Overgrowth
Undergrowth
Imprinting disorders:
Prader Willi Syndrome is characterized by ___, ____, and ____. Only maternal imprinting present.
Angela syndrome is characterized by seizures ataxia speech impairment. Only ____ imprinting present
Hypotonia, hyperphagia, hypogonadism
Paternal
Take home message
