Research Highlights

Is it possible to reverse the gene expression patterns associated with autistic syndrome?

2021-05-31 221

[POSTECH-Dankook University joint research team establishes a functional correlation between fragile X syndrome and BET-based proteins]


Autistic neurodevelopmental disorders or intellectual disabilities are known to be expressed by mutations of various genes. The fragile X syndrome (FXS), which is associated with autism, is sometimes accompanied by physical deformities such as long face and large feet, as well as developmental disorders such as delayed language development, social deficits, and hyperactivity. Recently, a research team has come up with a new way to alleviate FXS-related symptoms.

A research team led by POSTECH professors Tae-Kyung Kim and Seung-Kyoon Kim of the Department of Life Sciences with Professor Keunsoo Kang of the Department of Microbiology at Dankook University have together verified that functional abnormalities of bromodomain and extraterminal (BET) proteins involved in the expression of cancer or autoimmune diseases also contribute to the FXS. The study further demonstrated that that autism symptoms could be alleviated by selectively controlling the functions of these BET proteins. The findings of this research were published in Science Advances on May 19, 2021.

BET family proteins (BRD2, BRD3, BRD4, BRDt) are known to play an important role in the expression of various cancer cells and autoimmune diseases, acting as epigenetic regulators that control gene expression. The research team used various modern genomic analysis methods to detect changes that occur after selectively inhibiting the expression or function of all three major BET regulators, BRD2, BRD3, and BRD4 in normal neurons to determine their functional similarity or specificity in transcriptional regulation.*1 The study uncovered that the response of individual BET family proteins to a pan-BET inhibitor, JQ1 were widely different in neurons. Furthermore, applying the same analysis system to a mouse model of FXS together with behavioral experiments, the team confirmed that functional abnormalities of BET proteins could underlie FXS-related symptoms.


On the significance of the study, Professor Tae-Kyung Kim explained, “We have proposed a new approach to developing a molecular treatment for the fragile X syndrome, for which a treatment has not been clearly verified so far.” He added, “As each BET family member behaves differently, selectively controlling the function of each BET family protein could be an effective treatment strategy for severe autism like FXS with minimum side effects.”

This research was conducted with the support from the National Research Foundation of Korea and the Simons Foundation for Autism Research in the U.S.

1. Transcriptional regulation
Transcription is an intermediate step through which genetic information on DNA is expressed as a protein, and is the process of transferring gene information stored in DNA to messenger RNA (mRNA) by RNA polymerase. Proteins are made by translating this mRNA. The transcription of genes is essential for the survival and function of cells, and is regulated by a variety of mechanisms.