Topic 2B - Part 2 Flashcards
how does gene regulation in multicellular eukaryotes lead to cell specialization?
different types of cells express different genes
what is the first level of control in gene regulation?
the chromosome (before transcription takes place)
how does the chromosome level of control regulate gene expression?
the manner in which DNA is packaged can determine whether proteins necessary for transcription can gain physical access to the genes they transcribe
chromatin
a complex of DNA, RNA, and proteins that gives chromosomes their structure; chromatin fibres are either 30nm in diameter or, in a relaxed state, 10 nm
chromatin remodelling
the process in which the nucleosomes are repositioned to expose different stretches of DNA to the nuclear environment
can transcription proteins access DNA when chromatin is in its coiled state?
no
how is chromatin remodelled?
by chemical modification of the histones around which DNA is wound (usually histone tails)
histone tail
a string of amino acids that protrudes from a histone protein in the nucleosome
histone code
the pattern of modifications of the histone tails that affects the chromatin structure and gene transcription
what are the typical modifications of the amino acid lysine in the histone tail during histone modification?
additional of a methyl group (methylation) or acetylation (COCH3)
what is a common chemical modification to bases in DNA to regulate gene expression?
addition of a methyl group to cytosine
DNA methylation (ex. modification to base) recruits proteins that affects changes in:
chromatin structure, histone modification, and nucleosome positioning that restrict access of transcription factors to gene promoters
CpG Island
a cluster of CpG sites on a DNA strand where cytosine (C) is adjacent to guanosine (G) the ‘p’ represents the phosphate in the backbone; where cytosine methylation often occurs
heavy cytosine methylation is associated with:
transcriptional repression of the gene near the CpG island
undermethylated CpG islands allow:
transcription
heavy methylated CpG islands result in:
inhibition of transcription
epigenetic
describes effects on gene expression due to differences in DNA packaging; such as modifications in histones or chromatin structure
epigenetic mechanisms typically do not involve changes to:
DNA sequence itself, rather to the manner in which DNA is packaged
can epigenetic modifications be inherited?
yes, but they are often reversible and responsive to changes in the environment
imprinting
the sex-specific silencing of gene expression
for most genes, there is a direct relationship between:
the number of copies of the gene (gene dosage) and the level of expression of the gene
each copy of the gene is regulated ________ of other genes
independently
dosage compensation
the differential regulation of X-chromosomal genes in females and in males (regulation of genes in the X chromosome is different in females and males)
X-inactivation
the process in mammals in which dosage compensation occurs through the inactivation of one X chromosome in each cell in females
how does X-inactivation work?
a X chromosome contains the X-chromosome inactivation centre (XIC) which contains a gene Xist (X-inactivation specific transcript), Xist increases when X chromosome about to become inactive. transcript undergoes RNA splicing, Xist RNA coats the XIC region, coating spreads until entire chromosome is coated with Xist RNA which recruits factors that are associated with transcriptional repression
Xist RNA is an example of a:
noncoding RNA
if Xist gene is inserted into another chromosome…
that chromosome becomes inactivated
transcriptional regulation
the mechanisms that collectively regulate whether or not transcription occurs
what is the first point in transcription which regulates gene expression?
the recruitment of general transcription factors and components of the RNA polymerase complex (through the regulatory transcription factors)
regulatory transcription factor
a protein that recruits the components of the transcription complex to the gene
if the regulatory transcription factors do not recruit the components of the transcription complex to the gene,
transcription does not occur
silencers
DNA sequences that bind with regulatory transcription factors and repress transcription
if regulatory transcription factors bind with enhancers…
they stimulate transcription
if regulatory transcription factors bind with silencers…
they repress transcription
combinatorial control
regulation of gene transcription by means of multiple transcription factors acting together; a particular combination is needed of silencers/enhancers etc. to initiate transcription
what is an opportunity for regulating gene expression in RNA processing?
RNA splicing-alternative splicing allows primary transcript to yield different proteins
If exon 11 is missing in mRNA (ex. skeletal muscles):
cells form receptors with high insulin affinity
If exon 11 is present in mRNA (ex. liver cells):
cells form receptors with low insulin affinity
RNA editing
the process in which some RNA molecules become a substrate for enzymes that modify particular bases in the RNA, thereby changing it sequence and sometimes what it codes for
what happens if the amino group is removed and converted to inosine in adenosine?
the base functions like guanosine
what happens if the amino group is removed from cytosine?
it is converted to uracil
what is the result of RNA editing?
transcripts from the same gene can product multiple types of proteins even in a single cell
transcripts from the same gene may undergo different editing in different:
cell types (tissue specific)
small regulatory RNA
a short RNA molecule that can block transcription, cleave or destabilize RNAA, or inhibit mrNA translation; two types: siRNA and miRNA
small interfering RNA (siRNA)
a type of small double-stranded regulatory RNA that becomes part of a complex able to cleave and destroy single-stranded RNA with a complementary sequence
microRNA (miRNA)
small, regulatory RNA micromolecules that can cleave or destabilize RNA or inhibit its translation
siRNA and miRNA have different functions but similar:
forms of production; both are transcribed from DNA and form hairpin structures that are stabilized by base pairing
RISC (RNA-induced silencing complex)
a protein complex that is targeted to specific mRNA molecules by base pairing with short regions on the target mRNA, inhibiting translation or degrading the RNA
once small regulatory RNA is incorporated into RISC, depending on the type of small regulatory RNA, RNA sequence in RISC, and type of RISC, the small regulatory RNA may result in:
chromatin remodelling, degradation of RNA transcripts, or inhibition of mRNA translation
regulation by small RNAs in eukaryotes is thought to have originated as:
a defence against viruses and transposable elements
translation of mRNA into protein provides another level of:
control of gene expression
almost all mRNA molecules contain:
a 5’ cap, a 5’ untranslated region, an open reading frame (containing codons that determine the amino acid sequence of the protein), a 3’ untranslated region, and a poly(A) tail
the 5’ UTR and 3’ UTR (untranslated region) may contain:
regions that bind with proteins that help control mRNA translation and degradation, can also bind with small regulatory RNAs
how do proteins specify the certain places in a cell where mRNA can be translated?
by transporting the mRNA to particular regions of the cell (through RNA-binding proteins on UTR regions) or through repressing translation of mRNAs in specific locations
translation initiation is enhanced by:
poly(A) tail binding protein that brings the tail into contact with the initiation machinery on the 5’ cap-improves efficiency of translation initiation
what is one of the main recognition signals for translation initiation?
the 5’ cap structure where the translation machinery assembles
posttranslational modification
the modification, after translation, of proteins in ways that regulate their structure and function
what are protein chaperones?
act as folding facilitators for proteins once they come off the ribosome-important for acquiring stability
if folding is incorrect, protein may form:
aggregates that are destructive to cell function (ex. Alzheimer’s disease, Huntingdon’s disease)
the effect of an intervention-genetic or environmental- at any given level can affect:
regulatory processes at both higher and lower levels because expression of any gene is regulated at multiple levels
