Eukaryotic Gene Regulation II Flashcards
DNA methylation
ONLY silences gene transcription
histone methylation
can activate OR silence expression
H3K4me
activation of histone via methylation
H3K9me
silencing of histone via methylation
DNA methylation occurs on _
cytosines (C5) via DNA methyl-transferase
cytosine methylation occurs most commonly in _
context of CpG islands with the cytosines of both strands being methylated
MeCP2
recognizes methylated CpGs and recruits HDACs
methylation in cancerous cells
tumor suppressor genes are silenced via methylation
de novo methyltransferases
methylate completely unmethylated CpG –> expressed mainly in early embryo development and set up pattern of methylation
maintenance methyltransferases
add methylation to DNA when one strand is already methylated –> work throughout life to maintain pattern set by de novo methyltransferases
Rett syndrome symptoms
mental retardation, normal development until 1 years old, loss of speech and motor skills, seizures, microcephaly, ataxia, autism
Rett syndrome mutation
mutation in MeCP2 prevents binding to methylated DNA and no recruitment of HDACs –> causes locus to be turned on
MeCP2 is located _
on Xq28 (X chromosome)
What would happen if there was a mutation in MeCP2 in a male?
the male embryo would die because they only have one X chromosome –> the resulting phenotype would be too severe
MeCP2 duplication syndrome
extra copy causes silencing in other genes resulting in delayed motor skills and intellectual disabilities
embryo beta-globin locus
epsilon
fetus beta-globin locus
gamma-G and gamma-A
adult beta-globin locus
beta and delta
beta-thalassemia
beta-LCR deleted preventing transcription of the beta-globin locus
functions the locus control region
establish an open, active domain of chromatin, enhance transcription of genes within the domain, insulate negative effects of adjacent sequences
ligands that bind to nuclear receptors
cholesterol derivatives: testosterone, vitamin D3, retinoic acid, thyroxine, estradiol, cortisol
nuclear receptors
have ability to directly bind to DNA and regulate transcription
nuclear receptor mechanism
NR bound by HSP in absence of ligand (in cytoplasm) –> ligand binds –> HSP falls off and nuclear localization signal exposed –> receptors dimerize and go to nucleus –> find special DNA sequence –> bind –> transcription
androgen receptor (AR) ligands
5-DHT, testosterone, and 5-reductase
AR functions
- male sexual differentiation
- male behavior
- sperm production at puberty
- prostate development
- sex drive
AR gene regulation
protein synthesis, ligand binding, covalent modification, addition of second subunit, unmasking, and stimulation of nuclear entry
androgenetic alopecia
male-pattern baldness due to increased AR activities in hair follicles
spinal bulbar muscular atrophy (Kennedy’s disease)
neurodegenerative disease resulting from expanded CAG repeats in N-terminal domain of AR
AR is located on _
X chromosome
late-stage prostate cancer
AR mutations and amplifications
androgen insensitivity syndrome (AIS)
loss of function AR mutation –> genetically male but has physical traits of woman
