Researchers are identifying which elements of DNA influence MECP2 expression

Researchers at Baylor College of Medicine and the Jean and Dan Duncan Neurological Research Institute at Texas Children’s Hospital (NRI) identified and characterized two regions of DNA required for the correct expression of Mecp2 / MECP2 in mice and humans.

These results were published in Genes and development, In shedding light on the function of these DNA regions and how they might be potential targets for diagnostic and therapeutic interventions for intellectual disabilities such as Rett syndrome and MECP2 duplication syndrome.

Each of these intellectual disabilities are examples of how accurate MeCP2 levels are important to proper brain function. A decrease in this protein leads to Rett syndrome, while an excess of this protein leads to MECP2 complication syndrome. Both are acute neurological disorders characterized by learning disabilities, autistic characteristics and motor difficulties.

Dr Hoda Al Zoghbi, a professor at Baylor, director of NRI, and a researcher at Howard Hughes Medical Institute, emphasized the importance of understanding how the levels of RNA encoding this protein are regulated. Researchers in her lab have identified two regions of DNA that, upon mutation, lead to either a decrease or increase in MECP2 RNA and protein levels, resulting in the partial behavioral deficits observed in Rett’s syndrome and MECP2 duplication syndrome, respectively.

Yingyao Shao, the study’s first author and graduate student in the zombie laboratory, explains that when one of the two DNA regions was altered, the results showed a moderate decrease in MeCP2 levels mimicking the behavioral and molecular changes observed in Rett’s rat models. The alteration of the other DNA region caused a slight increase in MeCP2 protein levels similar to the rat models with double-expression of MeCP2.

“These results provide hope that future therapies targeting these DNA regions could have clinically relevant benefits, even when MeCP2 levels are slightly corrected,” said Shaw. “In addition, it is possible that mutations in either of these two regions of the DNA lead to intellectual disability or autism in humans, and therefore it is important to arrange these regions when examining the genetic causes of neurodevelopmental disorders,” Zoghbi added.


Among the other persons who contributed to this study, Dr. Samir S. Pajecar, and Harini B. Terumala, Manuel Canto Gutierrez, and Dr. Joshua de Wyeth, with the Jean and Dan Duncan Institute for Neurological Research and / or Baylor College of Medicine.

Funding provided by the National Institutes of Health (5R01NS057819 to HYZ, 1F32HD100048-01 to SSB), American Heart Association (19PRE34410104 to MCG), Institutional Startup Funds (JDW), Department of Defense (W81XWH-18-1-0350 to JDW), CIHR (PJT 155922 to JDW), Howard Hughes Medical Institute (HYZ), Baylor College of Medicine’s Intellectual and Developmental Disabilities Research Center (NIH 5P50HD103555), Henry Engel Fund and Ziff Family Fund.

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