Mendelian disorders of the epigenetic machinery: Tipping the balance of chromatin States

Jill A. Fahrner, Hans T. Bjornsson

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


Mendelian disorders of the epigenetic machinery are a newly delineated group of multiple congenital anomaly and intellectual disability syndromes resulting from mutations in genes encoding components of the epigenetic machinery. The gene products affected in these inherited conditions act in trans and are expected to have widespread epigenetic consequences. Many of these syndromes demonstrate phenotypic overlap with classical imprinting disorders and with one another. The various writer and eraser systems involve opposing players, which we propose must maintain a balance between open and closed chromatin states in any given cell. An imbalance might lead to disrupted expression of disease-relevant target genes. We suggest that classifying disorders based on predicted effects on this balance would be informative regarding pathogenesis. Furthermore, strategies targeted at restoring this balance might offer novel therapeutic avenues, taking advantage of available agents such as histone deacetylase inhibitors and histone acetylation antagonists.

Original languageEnglish (US)
Pages (from-to)269-293
Number of pages25
JournalAnnual Review of Genomics and Human Genetics
StatePublished - Aug 2014


  • DNA methylation
  • chromatin
  • epigenetics
  • epigenomics
  • histone tail modifications
  • therapeutic development

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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