Questions 6: Gene Expression Regulation (9 pts) Heart defectsfrom genetically inherited mutations affect about 1-2% of childrenand cause a significant number of stillbirths. They can also leadto heart disease in adults. Many genetically inherited heartdefects are due to mutations in genes for transcription factorsthat control expression of genes that are required for normal heartdevelopment. For example, over 30 different mutations have beenfound in the gene for transcription factor Tbx5 in patients withgenetically inherited heart defects. To carry out its functions,Tbx5 must bind to another transcription factor called Nkx2-5, whichalso plays a role in heart development and is mutated in manyindividuals with genetically inherited heart defects. Imagine thatyou can isolate developing cardiac cells with a Tbx5 mutation andstudy the molecular defects caused by the mutations. In each of thequestions I though III, please circle the correct multiple-choiceanswer and explain your reasoning - include an explanation for whyyour choice is correct AND a brief sentence or two explaining whythe other choices are incorrect.

I) In one mutant, you observe that the full-length “mature” Tbx5mRNA is present at its usual levels, but rather than full-lengthTbx5 protein being detected, a shorter version of it is detected.What kind of mutation most likely accounts for this phenotype?

A. A mutation that blocks binding of Tbx5 to Nkx2-5

B. A mutation that causes a splicing defect

C. A mutation that disrupts the normal folding of Tbx5

D. A mutation that introduces a premature stop codon

II) In another mutant cell line, you find that full-length Tbx5mRNA and protein are present at normal levels, yet individualscarrying this mutation have severe defects in heart development.What kind of mutation could cause this phenotype?

A. A mutation that blocks association of the Tbx5 mRNA with theribosome

B. A mutation that blocks export of the Tbx5 mRNA from thenucleus

C. A mutation that causes a splicing defect

D. A mutation that disrupts binding of Tbx5 with Nkx2-5

III) Which one of the following is a plausible mechanism bywhich Tbx5 could control initiation of transcription?

A. Activation of polyA tail addition

B. Recruitment of RNA polymerase to promoters

C. Recruitment of splicing factors to RNA polymerase

D. Regulation of 5’ cap formation