FMR1 Gene Regulation

With a $30,000 grant from FRAXA Research Foundation in 1999, Dr. Paul Hagerman and Dr. Flora Tassone at the University of California attempted to reactivate the FMR1 gene.

Paul Hagerman, PhD
$30,000 Grant
Paul Hagerman, PhD
Principal Investigator
University of California at Davis
1999 FRAXA Research Grant
$30,000 (1999)

FMR1 Gene Regulation

by Flora Tassone, 1/1/1999

Fragile X syndrome is usually caused by a large expansion of a CGG trinucleotide repeat in the FMR1 gene. Full mutations (greater than 200 repeats) are generally associated with methylation of CG-rich “islands” upstream of the gene. This expansion and subsequent methylation reduces or “silences” (turns off) transcription of the FMR1 gene so that it produces too little or none of its normal protein product (FMRP).

Studies with other human genes have provided evidence that methylation itself may not cause silencing of these genes. Rather, the methyl groups appear to act as signals for the modification of associated chromosomal proteins (histones) to a form that prevents transcription of these genes. Genes that are transcriptionally active (i.e., “turned on”) normally possess histones with acetyl groups attached. However, when a gene becomes methylated, enzymes called “histone deacetylases” are recruited to remove the acetyl groups from the histones near the gene. For a number of human genes, it has been shown that transcriptional activity can be at least partially restored by blocking the deacetylase with one or more drugs (histone deacetylase inhibitors). These inhibitors have not been examined in detail for the FMRI gene. In one phase of our investigations, a number of histone deacetylase inhibitors will be examined in cell culture for their ability to restore transcriptional activity of the FMR1 gene (turn the gene on). In a second phase of our research, quantitative methods for measuring FMR1 RNA levels will be used to better define the level of transcriptional activity.

Paul Hagerman, PhD

Explore Current Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Share via
Copy link