The X-Factor: Chromatin Remodeling Proteins
Image Credit: Image by Dr. Marian L. Miller (Journal-Cover-Art.com).
Fragile X Syndrome (FXS) is the leading genetic form of intellectual disability and autism, with males being more acutely affected than females. 1,2 Only a third of females with the syndrome have intellectual disabilities, while most males that have FXS are mildly or moderately disabled. The exact number of those with FXS is unknown, but it is estimated that 1 in 5000 males are born with it.3
It is a genetic Gordian knot, as the effects of a single defective gene, known as FMRP (Fragile X Mental Retardation Protein), reverberate through multiple chemical pathways, changing signals between the brain’s cells.
However, researchers at Rockefeller University have recently found that inhibiting the regulatory protein Chromatin in animal models alters the intricate signaling chemistry that is responsible for the disease’s symptoms. Their efforts focus on a group of proteins known as Chromatin Remodeling Proteins, which are already in clinical trials against a variety of cancers such as leukemia.4-6 The Chromatin Remodeling Protein is an appealing approach because the single inhibitor “releases” a proverbial tumbler of genetic “locks”. The intriguing findings of the Rockefeller researchers, led by Dr. Erica Korb, were published in Cell.7
3. B. Coffee, et al., Am J Hum Genet., 85(4), 503 (2009).
4. P.K. Davis and R.K. Brachmann, Cancer Biology & Therapy, 2:1, 23, (2003).
5. A. Wolffe, Oncogene, 20, 2988 (2001) doi:10.1038/sj.onc.1204322
6. C. Zhang, et al., Curr Protein Pept Sci., 17(5), 446 (2016).