The role of DNMT3B mutations in the pathogenesis of ICF syndrome

Sole Gatto, Maurizio D'Esposito, Maria R. Matarazzo

Research output: Chapter in Book/Report/Conference proceedingChapter


DNA methylation plays an important role in epigenetic signaling, having an impact on gene regulation, chromatin structure, development, and disease. The human genetic disease, called immunodeficiency, centromere instability, facial abnormalities (ICF) syndrome, is one example of the consequence of the impaired setting and maintenance of proper DNA methylation patterns. Here, we review the key properties of the mammalian de novo DNA methyltransferase DNMT3B, whose dysfunction is responsible for the ICF molecular phenotype, and take a closer look at the effects of the reported mutations on its methyltransferase activity. Moreover, we focus on the central role of DNMT3B in the epigenetic signaling network and the key questions still unsolved in the field, such as how this enzyme is targeted to specific genomic regions, leaving some others unmethylated, and how the DNA methylation pattern is modified during development and in response to environmental cues. The emerging models are multifaceted, involving both the intrinsic properties of DNMT3B and the influence of its interaction partners. In this regard, the ICF mutations provide us with a valuable model to understand the molecular properties of this DNA methyltransferase. The current knowledge and the proposed hypothesis about these topics will be summarized.

Original languageEnglish
Title of host publicationPatho-Epigenetics of Disease
PublisherSpringer New York
Number of pages27
ISBN (Print)9781461433453, 1461433444, 9781461433446
Publication statusPublished - Sep 1 2012

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)


Dive into the research topics of 'The role of DNMT3B mutations in the pathogenesis of ICF syndrome'. Together they form a unique fingerprint.

Cite this