transcription of genes is
regulated
expression of housekeeping genes is
constitutive
housekeeping genes usually have strong promoter and are efficiently and continuously
transcribed
housekeeping genes whose products are required at low levels have
weak promoter and are infrequently transcribed
________ ____ are expressed at different levels under different conditions
regulated genes
HAT
modify histones and open up DNA so other things can bind
gene expression is also regulated by ______ such as estradiol
hormones
the estrogen receptor is part of a larger class of regulatory proteins called ______ _____ ______
nuclear hormone receptors
nuclear hormone receptors are all activated by binding of small molecules or ligands and bind to specific regions of the DNA called
response elements
nuclear hormone receptors have two conserved domains which are
- the DNA binding domain
2. ligand binding domain
has zinc finger domains that confer specific DNA binding
DNA binding domain
ligand binding to the ligand binding domain causes a
structural change that enables the receptor to recruit other proteins to regulate transcription
coactivators and corepressors are recruited by
nuclear hormone receptors
proteins that bind the receptor after ligand binding are called
coactivators
ligand binding leads to structural rearrangements in the receptor that promotes
recruitment of additional proteins
_______ proteins bind to nuclear hormone receptors when ligand is absent to assist in repression of transcription
corepressor
ligands that activate a nuclear hormone receptor
agonists
ligands that inhibit the receptor
antagonists
some cancers require the estradiol-receptor complex, and growth of these cancers can be slowed by administering receptor antagonists such as
tamoxifen and raloxifene
good and bad effects of tamoxifen
good: decrease cancer and cholesterol; increase bone strength
bad: increase blood clots and uterine cancer
histone acetylation results in chromatin
remodeling
*how do coactivators stimulate transcription?
loosening the interactionbtwn histones and DNA, so the DNA is more accessible to transcription machinery
acetylation reduces the affinity of histones for
DNA
histone acetyllysine residues are interaction sites for many proteins which regulate ________, including factors which bind the TATA-box
transcription
acetyllysine residues also bind and recruit
chromatin remodeling proteins
histone acetylation is carried out by
histone acetyltransferases (HATS)
lysine residues can be
acetylated
histone acetylation ________ net positive charge - weakens interactions with other nucleosomes and proteins, loosens higher order structure
decreases
HATS directed to sites where chromatin must unravel to
transcribe a gene
histone deacetylases (HDCs)
remove acetyl groups - allow for re-compacting of DNA
in RNA processing of eukaryotes, large precursor RNA (45S) is processed to
18s, 28s, and 5.8s rRNAs…which are components of the ribosome
before cleavage, some bases and riboses are modified in a process catalyzed by RNA-protein complexes called
small nucleolar ribonucleoproteins (snoRNP)
tRNA endonucleases remove nucleotides from the
5’ end
tRNA nucleotidyl transferase* adds _____ to the ____ end
CCA; 3’
in prokaryotes the primary mRNA transcript is translated
directly
in eukaryotes transcription occurs in the
nucleus
in eukaryotes translation occurs in the
cytoplasm
splicing
in some mRNA pieces are removed from the middle and the ends joined
eukaryotic mRNA molecules have modified ends: eukaryotic mRNA precursors undergo modification to
increase their stability* and make them better substrates for translation
eukaryotic mRNA molecules have modified ends: ends are modified to they are no longer susceptible to
exonuclease degradation*
eukaryotic mRNA molecules have modified ends: the 5’ ends are modified (capped) before the mRNA precursors are completely
synthesized
addition of ___ required for splicing and other processing events
CAP
cap site is where _______ bind
ribosomes
cap is added by
gyanylyl transferase
poly A tails at the 3’ ends of ____ precursors
mRNA
eukaryotic mRNA precursors are also modified at their
3’ ends
a poly A polymerase adds up to ____ ____ residues to the 3’ end of the mRNA precursor
250 adenylate
poly a tail is progressively shortened by
3’ exonucleases
the poly A tail increases the time before nucleases reach
the coding region
sequences at the ends of introns specify
splice sites in mRNA precucrsors
most genes in eukaryotes consist of
exons and introns
introns
internal sequences that are removed from the primary RNA transcript.
exons
sequences that are present in the primary transcript and the mature mRNA
splice sites
junctions of the introns and exons where mRNA precursor is cut and joined
exons are joined by
splicing
small nuclear RNAs in splicosomes catalyze
splicing of mRNA precursors
defects in ______ may cause up to 15% of all genetic diseases
splicing
introns allow formation of alternative forms of a protein called
splice variants
alternative splicing is a powerful mechanism for expanding
protein diversity
in alternative splicing, a pre-mRNA can be splices in different patterns, generating proteins with
different funcitons
transcription and processing of mRNA are
coupled
transcription and splicing of mRNA are coordinated by the
carboxyl-terminal domain (CTD) or RNA pol 2
functions of the CTD include:
- recruit enzymes to synthesize the 5’ cap
- recruit components of the splicing complex
- recruit an endonuclease that cleaves the pre-mRNA to expose the site for poly A additio