Lecture 13 - Gene regulation in heart

Question 1

Cardiomyocytes only account for about ____% of the cells in the heart, but constitute most of the tissue mass because they are larger than the other cells.

Answer 1

30%

Question 2

Three main hallmarks of cardiac hypertrophy are increase transcription, increased translation, and ______ reorganization.

Answer 2

Sarcomere

Question 3

Acetylation is always associated with an ______ in gene transcription, while methylation can go both ways.

Answer 3

Increase

Question 4

If more _____pol II is bound to a gene than is observed in the normal heart, this suggests there was chromatin remodeling and an increase in transcription/gene expression.

Answer 4

RNA pol II

Question 5

Nppa and Nppb gene expression ______ during cardiac hypertrophy. These genes are not active in normal adult heart, but recruit RNA pol II for growth conditions.

Answer 5

Increase

Question 6

Transcription of Sip1 and Sec23a genes increased in growth conditions, but as a result of release of ____-paused RNA pol II.

Answer 6

Promoter

Question 7

With NELF and DSIF bound to RNA pol II, it caused the enzyme to pause. However, when NELF is phosphorylated by _____, RNA pol II does not pause.

Answer 7

CDK9

Question 8

There are 2 modes of gene transcription and 4 patterns identified from these modes in cardiac hypertrophy. Mode 1 = de novo RNA pol II ______ facilitated by ____IIB –> under normal conditions these genes are not expressed or are expressed at very low levels. Under growth conditions, significant increase in RNA abundance. Facilitated by phosphorylation of CDK__. Very small percent of genes are activated in this way (around 3%.) Mode 2 = promoter clearance –> under normal conditions, RNA pol II is paused at the promoter, but is released under growth conditions. This is facilitated by ____ and DSIF, both of which are normally negative elongation factors. ____ is phosphorylated by CDK9, which causes it to release from DSIF. At that point, DSIF switches from negative to positive elongation factor, and RNA pol II is cleared from the promoter. This results in an ______ increase in RNA –> this is found to occur in _____ genes (genes that are constitutively active for normal cell function.)

Answer 8

Recruitment

TFIIB

CDK9

NELF

NELF

Incremental

Housekeeping

Question 9

The difference between physiological cardiac hypertrophy vs pathological cardiac hypertrophy is that the latter can become _____ if unchecked.

Answer 9

Permanent.

Question 10

miRNA___ is the most abundant in the heart and regulates both TFIIB and Cdk9. _____-regulation of miRNA___ is required for cardiac hypertrophy.

Answer 10

miRNA-1

Down-regulation

miRNA1