Regulation of gene expression Flashcards
constitutive genes
genes that are expressed in all cells, all the time (housekeeping) ex: actin, tubulin, RNAP
regulated genes
genes with dynamic patterns of expression that can increase over time, respond to environmental signals, or oscillate with time or day/month
epigenetic modifications
mods to DNA or proteins that cause a stable and heritable alteration of gene expression or cellular function without changing the sequence of genomic DNA
DNA methylation
epigenetic mod, methylation of CpG islands near promoter gene regions decreases transcription of those genes
histone acetylation
epigenetic mod, acetylation of histones facilitates easier access to the DNA = active transcription; methylation of histones does not change charge of DNA but can recruit TFs so can have a + or - effect
monoallelic regulation of gene expression
gene activity depends upon whether an allele originated from a maternal or paternal gamete
if imprinted methylation occurs during gametogenesis in either mom or dad’s allele, that allele will not be expressed and only the other parent’s non-imprinted allele will be expressed. It is not understood why this occurs.
genomic imprinting
a subset of genes is differentially methylated depending upon parental origin; occurs on some genes clustered on chromosomes 11 and 15. Their expression is monoallelic due to the imprinting.
Errors in genomic imprinting cause PWS and AS
Certain microdeletions or duplications disrupt the normal imprinting process, causing two disorders called Prader-Willi syndrome (PWS) and Angelman syndrome (AS).
- *can result from uniparental disomy (when you receive 2 copies of part of a chromosome from the same parent and no copy from the other parent) in which case the imprinted allele for each parent is missing due to methylation and they get the disease.
- *or can result from microdeletions in the region in which the maternal or paternal allele is not present, and then the imprinted allele cannot become active either even though it’s there.
distal control elements
DNA sequences that are recognized and bound by regulatory factors that can affect transcription of nearby genes. Function in cis (independent of position, orientation, and distance). Includes enhancers, silencers, and response elements.
enhancers
DNA sequence (distal control element) that can activate gene transcription
silencers
DNA sequence (distal control element) that can suppress gene transcription
response element
DNA sequence (distal control element) that can act as either an enhancer or a silencer
activator
trans-acting; diffusible protein that can activate gene transcription by binding distal control elements
repressor
trans-acting; diffusible protein that can suppress gene transcription by binding distal control elements
transcription factors
subset of nuclear-localized DNA-binding proteins that function to affect gene transcription; includes activators, repressors, nuclear receptors
type 1 nuclear receptors
bind steroid hormones, located in the cytoplasm as monomers. Upon ligand binding, receptor dimerizes and transports to nucleus, binds response element and activates gene transcription
ex: estrogen, estrogen response elements
type 2 nuclear receptors
bind lipophilic hormones (i.e. thyroid hormone), located in the nucleus as an inactive heterodimer, bound to thyroid hormone response elements. Upon ligand binding, receptor compex is converted to a transcriptional activator
RNAi
RNA interference, inhibits gene expression by targeting specific mRNA sequences (inhibits translation of the gene product after transcription)
microRNA and siRNA (both double stranded) use base pairing to direct enzyme complexes to specific mRNAs and cause their degradation or prevent translation
XIST gene
encodes long non coding RNA (lncRNA) that deactivates the extra X chromosome in females causing formation of Barr bodies. X chromosome inactivation is initiated by expression of XIST RNA which coats the entire chromosome, deactivating it. Subsequent methylation of DNA and hypoacetylation of histones maintains the inactivation.
(however 15% of genes on inactive X chromosome escape inactivation)
X chromosome activation during embryogenesis
at ~200 cell stage, every cell randomly inactivates one X chromosome which stays silent except during meiosis/production of new haploid gametes.
**yields mosaic expression of X-linked genes
