Gene Expression

Question 1

What are 2 mechanisms of control in eukaryotic gene expression?

Answer 1

1. DNA Control elements

2. Transcriptional activators/repressors

Question 2

DNA control elements

Answer 2

part of DNA sequences, upstream or downstream. Acting in “cis” since they are on DNA.

Question 3

Transcriptional activators/repressors

Answer 3

proteins encoded by other genes. Proteins are made and then proteins diffuse through nucleus and activate/repress gene. Trans acting

Question 4

What is the DNA control element that the basal transcription machinery binds to?

Answer 4

TATA box

Question 5

Promoter proximal elements

Answer 5

DNA elements that are located slightly upstream from TATA box. Specific sites where cis acting factors bind to. Cell type specific. Can’t function if moved too far away.

Question 6

Enhancers

Answer 6

can be located upstream or downstream or in introns: regions that contain multiple control elements. Usually many base pairs away from promoter proximal elements

Question 7

3 diseases caused by mutations in DNA control elements

Answer 7

1. Thalassemias
2. Hemophilia B-leyden
3. Fragile C-syndrome

Question 8

Beta-thalassemia

Answer 8

mild inherited anemia (low hemoglobin count). Caused, here, by a mutation in the promoter of the b-globin gene, resulting in lowered rate of production of b-globin protein. (less promotion = less transcription) – associated with problems in the TATA box

Question 9

Hemophilia B Leyden-

Answer 9

X-linked disease (usually males) that affects clotting. Again, a problem in the promoter region of a clotting protein gene. Tends to get partially better at puberty

Question 10

Fragile X Syndrome

Answer 10

Again, usually a disease of men. Results in mental retardation and atypical development of the face with enlarged testicles (macroorchidism). Caused by an expansion in the CGG count upstream of a particular gene (the FMR1 gene), which results in an abnormally high rate of methylation in that region and transcriptional silencing of the gene.

Question 11

Describe the distinct functional domains of sequence specific DNA binding proteins.

Answer 11

Sequence specific DNA binding proteins are very modular (meaning the contain distinct domains that are separable). Usually contain DNA binding domain, activation domain, and flexible protein domain.

Question 12

The DNA binding domain of a sequence specific binding protein binds to:

A) Minor Groove
B) Major Groove
C) Proteins bound to DNA

Answer 12

B) Major groove

Question 13

Two kinds of transcriptional activators/repressors

Answer 13

1. Sequence specific DNA binding proteins

2. Co-factors

Question 14

4 common motifs within binding domains of sequence-specific transcription factors

Answer 14

1. Homeodomain
2. Zinc-finger
3. Basic Leucine Zipper
4. Helix-Loop-Helix

Question 15

3 diseases caused by mutations in various transcription factors:

Answer 15

1. Craniosyntosis
2. Androgen Insensitivity syndrome
3. Waardenberg syndrome type II

Question 16

Craniosyntosis

Answer 16

premature closure of the skull sutures in infants. Arises from a mutation in a homeodomain protein that causes the protein to bind more strongly, creating a “hypermorphic allele” that activates genes more strongly than it should. (upregulates proteins that close sutures via homeodomain mutation)

Question 17

Waardenburg Syndrome Type II

Answer 17

white streak of hair, wide face. 15% of cases result from mutation in MITF gene (encodes a bHLH (basic Helix-loop-helix) DNA binding protein), affects transcription of genes important for pigmentation and hearing
◾ deafness, pigmentation defects. Associated with mutations in the MITF (microphthalmia-associated transcription factor) gene (which codes for a bHLH binding protein that regulates melanocyte development).

Question 18

Androgen insensitivity syndrome

Answer 18

Feminization or undermasculinization. Indifference of androgen receptors to androgen hormones. Caused by a mutation in the zinc-finger androgen receptor binding domain or ligand binding domain. This downregulates the transcription of genes controlled by male androgens