Biochem Block 2 - Regulation Of Gene Expression

Front 1

All cells contain (same/different) set of genes

Back 1

same

Front 2

What are the advantages to regulating gene expression? (4)

Back 2

-cellular control over structure/function
-versatility and adaption
-conservation of energy (only need proteins produced - require high energy)
-different proteins made during development

Front 3

Transcription is regulated mostly on the level of _____

Back 3

-initiation

Front 4

The _____ consists of structural genes for proteins with related functions and require one ____

Back 4

-operon
-promoter

Front 5

______ prevent binding of RNA polymerase to the promoter through (positive/negative) control

Back 5

-repressor
-negative

Front 6

Repressors may be a constitutively active repressor, but some other repressors may require a _____ before become active

Back 6

corepressor

Front 7

Increased Trp inhibits transcription of Trp operson, so Trp acts as a _____ of Trp operson

Back 7

corepressor

Front 8

_____ stimulate transcription
What do these do?

Back 8

-inducers
-bind to promoter repressor and release it from promoter so that RNA polymerase can bind

Front 9

Inducers are usually _____

Back 9

nutrients or their metabolites

Front 10

Lac operon of E.coli encodes enzymes for _____ and is induced by _____
______ serves as an inducer through binding to the repressor

Back 10

-lactose metabolism (to glucose/galactose)
-lactose (no lactose, no need to make enzymes)
-lactose metabolite (allolactose)

Front 11

Presence of ______ prevents activation of lac operon

Back 11

glucose

Front 12

What happens in E coli with the presence of lactose and glucose?

Back 12

-Inducer, allolactose is produced, which inactivates the repressor
-High glucose = low cAMP (cAMP-CRP) is very low = low transcription
*cAMP-CRP is a coactivator

Front 13

What happens in E coli with the presence of lactose and absence of glucose?

Back 13

-Inducer, allolactose is produced, which inactivates the repressor
-low glucose = low cAMP, binds to CRP to make cAMP-CRP complex, which binds to operon and stimulates RNA polymerase binding and transcription

Front 14

How does high levels of Trp regulate attenuation of transcription?
Whats the difference if there is low Trp?

Back 14

-Ribosomes bind to transcript as it is being transcribed and rapidly translates an mRNA with a hairpin loop, which terminates transcription
-If there is low Trp, ribosomes transcribe the transcript slow, which produces a Trp that does not have a hairpin loop (no hairpin loop = no transcription)

Front 15

Eukaryotes (do/do not) have operons and each gene contains its own ______

Back 15

-do not
-promoter

Front 16

Genes change back and fourth from euchromatin to heterochromatin during:

Back 16

-development
-differentiation

Front 17

What is epigenetic code?
What are two examples of these?

Back 17

-changes in chromatin that can be inherited

Angelman syndrome - caused by maternally deleted and paternally imprinted genes on same genetic region

Prader-Wills syndrome (PWS) - caused by paternally deleted and maternally imprinted genes on same region

Front 18

What are the two mechanisms for chromatin remodeling?

Back 18

-ATP dependent - unwinds DNA from nucleosome (opens it up) to allow for binding of transcription factors
-Covalent modification of histones (see picture) - Histone acetyltransferase (HAT) aceylates Lys residue on tail of histone, which reduces electrostatic interaction. Histone deacetylases (HDAC) represses chromosome by changing back to amino
*Amino group has positive charge which increases interaction of DNA to histone, causing it to be more compact = no transcription

Front 19

Lipophilic hormones regulate transcription through ____
These consists of what domains? (4)

Back 19

-nuclear receptors (NRs - Gene specific TFs)

NRs consist of:
-Ligand binding domain - ions or molecules
-DNA binding domain
-Dimerization domain - other hormones
-Transactivation domain - binds coactivator

Front 20

_____ on DNA can be methylated to regulate DNA transcription
(hyper/hypo)methylation induces transcription while (hyper/hypo)methylation inhibits methylation
Cancer cells show global (hyper/hypo)methylation

Back 20

-Cytosine
-Hypomethylation induces
-Hypermethylation inhibits

-Cancer cells - hypomethylation

Front 21

Methylation of DNA regulates gene expression during _____

Back 21

differentiation (fetal development)

Front 22

For eukaryotes, transcription is usually regulated at the level of _____
Transcription is regulated by the assembly of _____, which is a complex of _____ and the additional transcription factors that binds to ______, which can increase transcription rate by _____ times and is located ______

Back 22

-initiation

-basal transcription complex
-TBP (TATA-binding protein and transcription factors complexed with RNA polymerase II)

-gene control regions
-up to 1000 times
-upstream or downstream

Front 23

Activators, inducers, repressors, or nuclear receptors contain what to regulate transcription?

Back 23

-DNA binding domain
-Domain for mediator proteins (coactivators, corepressors, or TBP-associated factors)
-Steroid hormone (can bind either corepressor or coactivator)
-Transcription Factors (TFs - can induce or inhibit transcription)

Front 24

How do glucocorticoids activate transcription?

Back 24

-Glucocorticoid receptor (GR) binds to CORTISOL in CYTOSOL
-GR dissociates from HSP, exposing NLS and forms a dimer
-dimer translocates into nucleus and binds to glucocorticoid response element (GRE)
-Transactivating domain binds to coactivator, initiating transcription

Front 25

How do the heterodimer thyroid hormone (TR) and retinoid X receptor (RXR) regulate transcription?

Back 25

-heterodimer is bound to DNA
-without thyroid hormone, it binds to corepressor and inhibits transcription
-with thyroid hormone, hormone binds to TR and causes conformation change and binds to coactivator, causing transcription
*HDAC attaches to corepressor (HDAC causes nucleosomes and DNA to be tightly bound)

Front 26

What is androgen insensitivity disease (AIS)?
What happens when a woman has complete AIS?
Incomplete AIS can lead to what? (2)

Back 26

-patient can produce androgens, but lack its receptors
-normal female body except for 46XY chromosome

Can lead to:
-Gynecomastia - breast in men
-Cryptochidism - one or both testes do not descend from scrotum after birth

Front 27

Transcription factors (TFs) can also regulate level transcription. In what ways do TFs regulate transcription?

Back 27

-levels of TFs
-binding of inhibitor or stimulator
-stimulation of nuclear entry
-phosphorylation (CREB by PKA or MAP kinase)

Front 28

In splicing or mRNA, (exons/introns) are "junk DNA, and (exons/introns) read to make protein
This results in:
The most common type of splicing is

Back 28

-introns
-exons

-diverse set of proteins from limited genes

-exon skipping

Front 29

apoB mRNA is an example of splicing and can be found in:
Intestinal apoB has been found to:
apoB _____ are more prone to atherosclerosis and apoB _____, and animals with low or no _____ apoB editing activity have higher levels of ____

Back 29

-liver and intestines

-more efficient fat absorption

-apoB100 than apoB48

-no hepatic apoB mRNA editing = high levels of VLDL/LDL

Front 30

Gene expression can also be regulated through mRNA degradation. What are the two ways this happens?

Back 30

-shortening of polyA tail (mRNA turnover) - loss of tail leads to exosome from 3' end

-decapping - degraded from 5' end

Front 31

What does transferrin receptors do and how is it regulated?

Back 31

-Transferrin receptor takes up transferrin which is a iron transporter in blood
-High iron = no need for receptors - iron binds to IRE-BP and releases mRNA and mRNA is degraded
-Low iron = want for more receptor - IRE-BP binds to IRE and prevents degradation of mRNA

Front 32

What is ferritin and how is it regulated?

Back 32

-Ferritin is main storage protein of iron
-Low iron = no need for ferritin - Iron does not bind to IRE-BP near 5' end and stays bound to mRNA to prevent translation
-High iron = need ferritin - Iron binds to IRE-BP and dissociates from mRNA to initiate translation of ferritin

Front 33

In prokaryotes, regulation of gene expression occurs through:

Back 33

-induction and repression of transcription (repressors, inducers, corepressors, coactivators)

Front 34

In eukaryotes, regulation of gene expression occurs through:

Back 34

-chromatin modification and remodeling (HAT and HDACs/DNA and histone methyltransferases)
-regulation of transcription initiation (positive and negative transcription factors)
-level of translation (mRNA editing/mRNA degradation/binding of ribosome to mRNA)