Question

1. (4 pts) As described in lecture, thyroid hormone receptor (TR) can activate or repress gene expression.  The malic enzyme(ME) gene contains multiple thyroid response elements (TRE) in its regulatory region and is regulated by TR.  Based on the description of how TR regulates gene expression, explain how the following conditions will affect the expression of the ME gene compared to the expression levels that would be observed when thyroid hormone (T3) is present (i.e. would expression be higher, lower, or about the same).  You may assume that all of the cells contain similar levels of TR and other regulatory proteins (the only differences will be caused by the conditions indicated below).  Explain your answers in the context of ME gene expression in the presence of T3.

1. No T3 present.
2. T3 present. Cells treated with an inhibitor of histone deacetylases.  
3. T3 present. Cells treated with an inhibitor of histone acetylase transferases.  

Grading: 1 pt for explaining how TR regulates expression of the ME gene in the presence of T3; 0.5 pt each for clearly indicating whether gene expression levels will increase, decrease, or stay the same for each condition; 0.5 pt each for explaining why each condition would result in those relative expression levels.

Answer 1

Thyroid hormone is a steroid hormone, this directly cross the plasma membrane. And inside the cell it again transpired with the transporter pritein , upon entering in the nucleus it binds with its thyroid receptor which I'd already present in bind form at TRE. As thyroid binds at TR this lead to activation of TRE by recruiting histone acetyl transfers. This cause transfer of acetyl group to histone and convert heterochromatin to euchromatin and increase expression of gene.

So based on this knowledge we can easily give answers if the question

1) in case of No T3, no activation of thyroid receptor present at TRE no recruitment of Histone acetyl transferase-- no expression of ME gene or expression remain same as previously

2) T3 present, treated with histone deacetylase inhibitor

Lead to activation of or expression or increase expression of ME gene.

As T3 will bind to TR and activation of TRE and increase expression of gene. Further there is inactivation of histone deacetylase also supports expression of ME gene

Histone deacetylase- removes acetyl group from histone and convert euchromatin to heterochromatin. Cause decreased gene expression.

3) T3 plus treated with inhibitor of histone acetylase teanferase - gene expression will decrease

As after binding of Thyroid hormone to thyroid receptor, lead to recruitment of Histone acetylase transferase. Cause activation of gene expression here we are using inhibitor of histone acetylase transferase so this will lead to interfere in conversion of heterochromatin to euchromatin and decrease gene expression.