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Role of conserved cis-regulatory elements in the post-transcriptional regulation of the human MECP2 gene involved in autism

Joetsaroop S Bagga13 and Lawrence A D’Antonio2*

Author Affiliations

1 John P. Stevens High School, 855 Grove Ave., Edison, NJ 08820, USA

2 Ramapo College of New Jersey, 505 Ramapo Valley Rd., Mahwah, NJ 07430, USA

3 Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, PA 15213, USA

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Human Genomics 2013, 7:19  doi:10.1186/1479-7364-7-19

Published: 16 September 2013



The MECP2 gene codes for methyl CpG binding protein 2 which regulates activities of other genes in the early development of the brain. Mutations in this gene have been associated with Rett syndrome, a form of autism. The purpose of this study was to investigate the role of evolutionarily conserved cis-elements in regulating the post-transcriptional expression of the MECP2 gene and to explore their possible correlations with a mutation that is known to cause mental retardation.


A bioinformatics approach was used to map evolutionarily conserved cis-regulatory elements in the transcribed regions of the human MECP2 gene and its mammalian orthologs. Cis-regulatory motifs including G-quadruplexes, microRNA target sites, and AU-rich elements have gained significant importance because of their role in key biological processes and as therapeutic targets. We discovered in the 5′-UTR (untranslated region) of MECP2 mRNA a highly conserved G-quadruplex which overlapped a known deletion in Rett syndrome patients with decreased levels of MeCP2 protein. We believe that this 5′-UTR G-quadruplex could be involved in regulating MECP2 translation. We mapped additional evolutionarily conserved G-quadruplexes, microRNA target sites, and AU-rich elements in the key sections of both untranslated regions. Our studies suggest the regulation of translation, mRNA turnover, and development-related alternative MECP2 polyadenylation, putatively involving interactions of conserved cis-regulatory elements with their respective trans factors and complex interactions among the trans factors themselves. We discovered highly conserved G-quadruplex motifs that were more prevalent near alternative splice sites as compared to the constitutive sites of the MECP2 gene. We also identified a pair of overlapping G-quadruplexes at an alternative 5′ splice site that could potentially regulate alternative splicing in a negative as well as a positive way in the MECP2 pre-mRNAs.


A Rett syndrome mutation with decreased protein expression was found to be associated with a conserved G-quadruplex. Our studies suggest that MECP2 post-transcriptional gene expression could be regulated by several evolutionarily conserved cis-elements like G-quadruplex motifs, microRNA target sites, and AU-rich elements. This phylogenetic analysis has provided some interesting and valuable insights into the regulation of the MECP2 gene involved in autism.

G-quadruplex; Post-transcriptional regulation; MECP2; MicroRNAs; AU-rich elements; Autism