Transcription 2

Question 1

There are two classes of chromatin remodelling factors - what are they and how do they work?

Answer 1

DNA -dependent ATPases (SWI/SNF) work by disrupting histone octamers and DNA. HATS and HDACS reversibly modify histones through acetylation.

Question 2

What type of base is abundant in the histone N-terminus that can be modified by acetylation/methylation, etc.?

Answer 2

Lysine Residues.

Question 3

Activators and repressors recruit which two factors?

Answer 3

HATS and HDACs.

Question 4

Name the chromatin remodelling factor that works by neutralizing the positively charged ends of histones through acetylation, thus opening the nucleosomal DNA for transcription factors/Pol II?

Answer 4

Histone Acetyltransferases (HATS)

Question 5

Name the Chomatin remodelling factor that works against HATS to maintain positive charges and prevent access to the promoter.

Answer 5

Histone Deacetylases (HDACs)

Question 6

What molecule is a co-activator for transcription on the histone?

Answer 6

HATS

Question 7

What molecule is a co-repressor for transcription on the histone?

Answer 7

HDACs

Question 8

Rubinstein-Taybi Syndrome. What is it, and what molecule is missing?

Answer 8

It is a multisystem disorder characterized by mental and growth retardation, craniofacial dysmorphism, and abnormally broad thumbs and great toes. It is linked to a lack of a HAT for the CREB binding protein (CBP) gene.

Question 9

Leukemia - itÍs a hematopoietic malignancy. What is this caused by?

Answer 9

Gain of function mutations occur on transcriptional regulators such as HATS and HDACs, altering their activity.

Question 10

What are four mechanisms for regulating DNA binding proteins?

Answer 10

1. Conformation change by ligand binding. 2. Regulation of entry into the nucleus. 3. Transcription factors can be regulated. 4. DNA binding can be regulated. 5. phosphorylation can alter properties (protein degradation, recruitment of co-activators, DNA binding).

Question 11

What family of DNA binding protein works as a transcription factor by binding steroid hormones?

Answer 11

Zinc Finger - displays how ligand binding can affect DNA binding proteins.

Question 12

The estrogen receptor is induced to dimerize and activate transcription through addition of estrogen to what structure on the receptor?

Answer 12

Zinc Finger.

Question 13

Explain tamoxifan’s action on the Estrogen Receptor.

Answer 13

Tamoxifan antagonizes estrogen by binding to ER and preventing recruitmentof HAT co-factors.

Question 14

NF-kB normally binds to IkB which masks its normal signal. What event precipitates breakdown of IkB and the movement of NF-kB into the nucleus to turn on target genes in inflammation?

Answer 14

Phosphorylation of the IkB.

Question 15

High intracellular calcium increases transcription of immune responseand heart function genes through what mechanism?

Answer 15

Calcium activates calcineurin’s phosphatase activity which dephosphorylates cytoplasmic NF-AT. This allows NF-AT into the nucleus where it affects transcription of those genes.

Question 16

What two immunosuppressants normally act by inhibiting NF-AT action through calcinuerin?

Answer 16

cyclosporin and FK506

Question 17

Beta catenin is normally broken down via phosphorylation by Glycogen Synthase 3 (GSK3) with Axin and APC. Explain how this is changed to allow Beta catenin to enter the nucleus.

Answer 17

Wnt signaling destabilizes the Axin-APC-GSK3 complex, increasing the pool of Beta catenin. This allows it into the nucleus to promote the expression of Wnt responsive genes.

Question 18

What is downregulated by binding the MDM2 protein, masking the activation domain and marking it for destruction by ubiquitin-proteasome pathway?

Answer 18

p-53; important in cancers; this is an example of regulating the amount of transcription factor in a cell.

Question 19

How do ID proteins work?

Answer 19

Id proteins negatively regulate DNA binding by heterodimerizing with other HLH proteins but preventing DNA binding (they are basic).

Question 20

How is CREB regulated by phosphorylation?

Answer 20

CREB (cyclic AMP response element-binding protein) - is inactive until phosphorylated; once it is active, it recruits HATs and RNA Pol II, activating transcription on the gene.