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Contribution of spurious transcription to intellectual disability disorders
  1. Marilyn Scandaglia,
  2. Angel Barco
  1. Molecular Neurobiology and Neuropathology Unit, Instituto de Neurociencias (UMH-CSIC), San Juan de Alicante, Alicante, Spain
  1. Correspondence to Dr Angel Barco, Molecular Neurobiology and Neuropathology Unit, Instituto de Neurociencias (UMH-CSIC), San Juan de Alicante, Alicante, Spain; abarco{at}


During the development of multicellular organisms, chromatin-modifying enzymes orchestrate the establishment of gene expression programmes that characterise each differentiated cell type. These enzymes also contribute to the maintenance of cell type-specific transcription profiles throughout life. But what happens when epigenomic regulation goes awry? Genomic screens in experimental models of intellectual disability disorders (IDDs) caused by mutations in epigenetic machinery-encoding genes have shown that transcriptional dysregulation constitutes a hallmark of these conditions. Here, we underscore the connections between a subset of chromatin-linked IDDs and spurious transcription in brain cells. We also propose that aberrant gene expression in neurons, including both the ectopic transcription of non-neuronal genes and the activation of cryptic promoters, may importantly contribute to the pathoaetiology of these disorders.

  • intellectual disability
  • histone posttranslational modification
  • DNA methylation
  • gene silencing
  • cryptic promoters
  • ectopic expression

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  • Contributors MS and AB revised the literature and wrote the manuscript.

  • Funding MS was the recipient of a ‘Formación de Personal Investigador’ fellowship from the Spanish Ministry of Science, Innovation and Universities (MICINN). AB research is supported by grants SAF2017-87928-R, PCIN-2015-192-C02-01 (part of the ERA-NET NEURON JTC2015 project ChromISyn) and SEV-2017-0723 from MICINN cofinanced by ERDF, grant PROMETEO/2016/026 from the Generalitat Valenciana, and grant RGP0039/2017 from the Human Frontiers Science Program Organization (HFSPO). The Instituto de Neurociencias is a ‘Centre of Excellence Severo Ochoa’.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Not required.