Question

Retinitis pigmentosa is a genetic disease that causes the breakdown and loss of retinal cells. Retinitis pigmentosa often starts with decreased night vision and will progress to blindness as retinal cells die.

Several genes have been linked to Retinitis pigmentosa, one of which is GADD. Mice lacking GADD (these mice were experimentally created so that the GADD region of the genome was deleted) have increased expression of non-retinal genes in retinal cells. In other words, in these mutant mice, genes that are not normally expressed in the retina are expressed.  

Crx is a key retinal transcription factor. Crx binds regulatory elements called CBRs (Crx-binding regions). GADD has two CBRs, one immediately proximal to the transcription start site (TSS), and one a few hundred base pairs downstream of the TSS.

You have received DNA from three patients with Retinitis pigmentosa. From the DNA, you sequence the GADD gene and its proximal/core promoter region.   

None of the patients have mutations in the coding region of GADD. All of the mutations you find are in the CBRs. Your findings are below:

• Patient 1 – Mutation in CBR1
• Patient 2 – Mutation in CBR2
• Patient 3 – Mutation in CBR1 and CBR

If you compared histone acetylation in the GADD CBRs between retinal cells and cheek cells would you expect to see more histone acetylation in retinal cells or cheek cells? Explain your answer.

To clarify, the question is asking you to compare histone acetylation in normal cells (normal retinal, and normal cheek), not in people with the disease or in the knock-out mice.

Answer 1

To answer this you have to remember what acetylation of histones does to the respective DNA expression. Acetylation tends to up regulate the region's expression, so an acetylated region will be the one that will constantly express in the respective cells.

Now, GADD CBRs are needed to correctly express retinal genes and develop functional retinal cells. In this case, we expect to see more histone acetylation in GADD CRBs in retinal cells than in cheek cells, because such acetylation leads to support the expression of CBRs in them.