Epigenetics and Gene Regulation

Flashcards covering important terms and concepts related to epigenetics and gene regulation.

epigenetics

stably inherited phenotypes and processes that result from alterations in chromatin structure that do NOT alter the DNA sequence

Epigenesis

how an embryo develops

Genetics

study of genes and heredity

transgenerational

Epigenetic alterations persist across many cell divisions and multiple generations of offspring

Environmental factors

can influence epigenetics

Epigenome

overall pattern of chromatin modifications possessed by each individual organism

Chemical modification of histone proteins

Histone modifiers add or remove chemical groups (phosphates, methyl groups, acetyl groups to histones)

Changes in patterns of DNA methylation

Methylation of cytosine bases (5-methylcytosine- 5meC) usually represses transcription

Noncoding RNAs that affect chromatin structure

Example: X-inactivation is initiated by Xist (a long noncoding RNA)

histone structure

an N-terminal tail of 11 – 37 positively-charged amino acids [lysine (K) and arginine (R)] that can have chemical modifications

Acetylation and methylation

happens mainly histones H3 and H4

Most frequent site of acetylation

Lysine (K)

Most frequent site of methylation

lysine and arginine (R)

Histone code

Multiple chemical modifications are required for open chromatin →

closed chromatin and vice versa

Effects of modifications

change the net charge of histone tail and affect

interactions with negatively-charged DNA

Charge of Lysine and arginine

positively-charged R groups

Methylation (in histones)

can activate or repress transcription (depends on gene or location of methylation)

Acetylation

usually activates transcription

histone methyltransferases (HMTs)

Addition of methyl groups

histone demethylases (HDMTs)

Removal of methyl groups

histone acetyl transferases (HATs)

Addition of acetyl groups

histone deacetylases (HDACs)

Removal of acetyl groups

Unmethylated DNA

relaxed chromatin; transcriptionally active

Methylated DNA

heterochromatin; transcriptionally silenced

DNA methyltransferases (DNMTs)

add methyl groups

Demethylases

remove methyl group

hemimethylated

Newly-replicated DNA that has the template strand methylated but the new strand lacks methylation

Maintenance DNMTs

recognize hemimethylated DNA and add methyl groups to C on the

newly strand strand during replication

De novo DNMTs

do not require hemimethylated DNA but are recruited to specific

sequences and are involved in regulation of transcription

Bisulfite sequencing

Used for detection and quantification of 5-meC

Chromatin immunoprecipitation (ChIP) assays

Used to identify DNA sequences bound by a specific protein

vernalization

a prolonged cold period required by some plants before they flower

FLC

negative regulator of flowering; no flowering happens when expressed

flc mutant

plants flower without vernalization

Flowering locus D (FLD)

represses the transcription of FLC

ChIP and its use on FLC

used to quantify the histone modifications in a fld mutant plant

X-inactivation

the mechanism for dosage compensation in placental mammals; monoallelic expression of X-linked genes

Xist,

X inactivation specific transcript; expressed from the inactive X but is not expressed on the active X

Dizygotic twins

nonidentical twins; two different eggs were fertilized by two different sperm

Monozygotic twins

identical twins; One egg was fertilized by one sperm, and the embryo splits into two identical embryos

Concordant trait

trait is shared by both members of a twin pair

Concordance

percentage of twin pairs that are concordant for a trait

High difference in monozygotic versus dizygotic concordance

generally implies that the trait is genetically influenced; usually monozygotic twins have a higher concordance %

The Dutch Hunger Winter

a mass starvation during WWII that affected the Dutch; lead to an epigenetic shift that affected children born after the starvation

Temperatuer that determines males in turtles

26 degrees C and lower

Temperatuer that determines females in turtles

32 degrees C and higher

26 degree C

High Dmrt1 expression in embryonic gonads; male

32 degree C

Low Dmrt1 expression in embryonic gonads; female

DNA Methylation on Dmrt1

silences Dmrt1 promoter → does not allow male specific genes → influenced by temperature

Kdm6b

lysine-specific histone demethylase

Demethylization of histones (Turtles)

silences transciption (does not allow male gene expression)