MCB Exam 2 Tutor Slides

Gene Regulation requires ___ sequences and Gene Regulatory proteins.

DNA

What is the DNA recognition sequence?

GATA

Regulatory proteins bind to DNA’s _____ groove.

major

Transcription ____ have different modules/units.

factors

This binds major groove and has 2 alpha helices.

Helix-turn-Helix

This binds to major groove and has a zinc DNA binding motif.

Zinc finger

This has 2 alpha helices and forms dimer and has leucine residue every 7 amino acids.

Leucine Zipper

This has 2 alpha helices and forms a loop.

Helix-loop-Helix

What is caused by a zinc finger transcription factor mutation and results in unstable RBC’s that lyse and release hemoglobin with symptoms of hemolysis, anemia, and splenomegaly?

Hereditary Spherocytosis

KLF1 is a ___ ____ TF → mutation impairs DNA binding → ↓ expression of RBC membrane-skeleton genes (alpha spectrin, beta spectrin, ankyrin) → hereditary spherocytosis.

Zinc finger

What do activators do that can make DNA more accessible?

Nucleosome remodeling, Nucleosome removal, Histone replacement, Histone modification/acetylation

Open/accessibile chromatin → ↑ _______

transcription

What are the six mechanisms that are how repressors turn genes off?

Compete with activator for binding site, mask activator's activation domain, block general transcription-factor assembly, recruit chromatin-remodeling complexes, recruit histone deacetylase, recruit histone methyltransferase

Block the activator → block the transcription machinery → close the _____

chromatin

What are the ways that gene regulatory proteins can be controlled?

Synthesis, ligand binding, phosphorylation/covalent modification, addition of another protein subunit, unmasking an active domain, entry into the nucleus, proteolysis

A transcription factor can already exist in the cell but still be inactive until something ______ it

activates

Increasing ____ hemoglobin can benefit sickle- cell disease.

fetal

What makes different proteins with the same pre-mRNA with different exon combinations?

Alternative splicing

What is mRNAs have different half-lives (globin = 10 hrs), 5’ cap and poly-A tail protect RNA, and Poly- A shortening → degradation?

mRNA stability

What are small regulatory RNA that are processed to mature ____, associates with Argonaute/RISC, which lowers target gene expression by: inhibiting translation and/or promoting mRNA degradation?

miRNA

miRNA involvement was found in 1 type of _____ ____, a variant of SLITRK1 gene, where a change in recognition sequence SLITRK1 mRNA increased miRNA binding

Tourette’s Syndrome

What protein brings iron into cell?

transferrin receptor

What protein stores iron?

Ferritin

What is a RNA element that IRP binds?

IRE

What means low iron?

IRP binds IRE, Ferritin 5′ IRE → translation blocked → ↓ ferritin, TfR 3′ IREs → mRNA stabilized → ↑ TfR→ Bring iron in; don't store it

What means high iron?

Iron binds IRP → IRP no longer binds IRE, ↑ ferritin, TfR mRNA degraded → ↓ TfR

What ways are proteins regulated after translation?

folding/chaperones, cofactor binding, phosphorylation, glycosylation, association with other protein subunits, proteolytic cleavage

Protein made ≠ protein necessarily ____

active

Ubiquitin pathway: E1 → E2 → E3 → ubiquitin-tagged protein → _____

proteasome

What does E1 do?

activates ubiquitin

What does E2 do?

carries ubiquitin

What does E3 do?

recognizes the target

Proteasome destroys the ____ protein.

tagged

___ provides target specificity

E3

What is a reversible proteasome inhibitor, used for multiple myeloma, and prevents degradation of pro-apoptotic proteins that promote apoptosis?

Bortezomib

A ____ protein can control a battery of downstream genes, allows coordinated response to a physiological need, an example being cortisol?

regulatory

Cells contain the same ___

genome

Different combinations of regulatory proteins turn different genes on/off, for different proteins, different specialized cell types. What is an example?

Hematopoietic stem cell → different blood- cell lineages

What is covalent modification of DNA and associated here with repression of gene expression?

DNA methylation

What is gene expression depends on parent of origin and one parental allele may be epigenetically silenced?

Genomic imprinting

What is the paternal deletion of on chromosome 15 that results in symptoms of Stage 1: Infantile hypotonia, poor suck/feeding difficulties, failure to thrive and Stage 2: Hyperphagia (uncontrollable eating), childhood obesity?

Prader Willi Syndrome

What is the paternal gene copy that is deleted in Prader-Willi syndrome that results in the mom’s copy still there but it is silenced so that the cell ends up with no working expression of those genes?

Genes in 15q11-q13 that is on from dad and off from mom because of imprinting

What is when dosage compensation helps equalize X-linked gene expression between males and females, early in development, on X chromosome in each female cell is inactivated, it becomes highly condensed heterochromatin aka a Barr Body, it is random, some cells inactivate the maternal X, some cells inactivate the paternal X, and females are mosaics of cells with different active X chromosomes?

X chromosome inactivation

Random X-inactivation → one active X per cell → dosage compensation + female _____.

mosaicism