You have found a mutant mouse that does not express gene K in pancreatic beta ce

Question

You have found a mutant mouse that does not express gene K in pancreatic beta cells. You sequence gene K in the mutant and there are no mutations in the transcribed region or promoter. Southern blot using probes to regions around your gene reveals that there is a 9kb deletion 70kb away from gene K. You perform RT-PCR to look at expression of other genes near gene K. You find that there are 5 genes (F-J) near gene K that are transcribed in beta cells from normal animals but not expressed in the mutant cells. There are 4 genes on the other side of the deletion (A-D) from gene K that are not expressed in mutants or wild type mice. When you analyze chromatin state , you find that A-D are heterochromatic in WT and mutants. F-K are euchromatic in WT and heterochromatic in the mutant. What was deleted in the mutant that led to the observed changes?

Explanation / Answer

In the wild type mice, A-D are heterochromatinized which means that the genes in this region are not expressed as the DNA is highly condensed in this region due to the interaction of the negatively charged DNA with the positively charged histones that together make up the nucleosome and higher order chromatin structures.

A similar situation is present in the mutant mouse.

However in the case of genes F-K, in the wild type mouse they are euchromatinized while in the mutant mouse they are heterochromatinized. This is due to the fact that their is a 9kb deletion 70kb away from the gene K in mutant mouse.

This region is a regulatory sequence which allows for various Histone modifiers and active Chromatin remodellers to bind to and decompress the DNA condensation thus allowing various transcription factors to come and activate the downstream genes as is the case in the wild type.

In the mutant, this region is deleted which does not allow the active chromatin remodellers to bind to the DNA and decompress it so Trans acting factors cannot bind the downstream promoter sequences.

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