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

3 Citations (Scopus)

Abstract

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
Pages15-41
Number of pages27
Volume9781461433453
ISBN (Print)9781461433453, 1461433444, 9781461433446
DOIs
Publication statusPublished - Sep 1 2012

Fingerprint

Methyltransferases
DNA Methylation
Epigenomics
Mutation
Inborn Genetic Diseases
Centromere
DNA
Medical Genetics
Chromatin
Cues
Maintenance
Phenotype
Enzymes
Genes

ASJC Scopus subject areas

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

Cite this

Gatto, S., D'Esposito, M., & Matarazzo, M. R. (2012). The role of DNMT3B mutations in the pathogenesis of ICF syndrome. In Patho-Epigenetics of Disease (Vol. 9781461433453, pp. 15-41). Springer New York. https://doi.org/10.1007/978-1-4614-3345-3_2

The role of DNMT3B mutations in the pathogenesis of ICF syndrome. / Gatto, Sole; D'Esposito, Maurizio; Matarazzo, Maria R.

Patho-Epigenetics of Disease. Vol. 9781461433453 Springer New York, 2012. p. 15-41.

Research output: Chapter in Book/Report/Conference proceedingChapter

Gatto, S, D'Esposito, M & Matarazzo, MR 2012, The role of DNMT3B mutations in the pathogenesis of ICF syndrome. in Patho-Epigenetics of Disease. vol. 9781461433453, Springer New York, pp. 15-41. https://doi.org/10.1007/978-1-4614-3345-3_2
Gatto S, D'Esposito M, Matarazzo MR. The role of DNMT3B mutations in the pathogenesis of ICF syndrome. In Patho-Epigenetics of Disease. Vol. 9781461433453. Springer New York. 2012. p. 15-41 https://doi.org/10.1007/978-1-4614-3345-3_2
Gatto, Sole ; D'Esposito, Maurizio ; Matarazzo, Maria R. / The role of DNMT3B mutations in the pathogenesis of ICF syndrome. Patho-Epigenetics of Disease. Vol. 9781461433453 Springer New York, 2012. pp. 15-41
@inbook{7bfbac2fa68d4d3ab9b473426d298046,
title = "The role of DNMT3B mutations in the pathogenesis of ICF syndrome",
abstract = "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.",
author = "Sole Gatto and Maurizio D'Esposito and Matarazzo, {Maria R.}",
year = "2012",
month = "9",
day = "1",
doi = "10.1007/978-1-4614-3345-3_2",
language = "English",
isbn = "9781461433453",
volume = "9781461433453",
pages = "15--41",
booktitle = "Patho-Epigenetics of Disease",
publisher = "Springer New York",

}

TY - CHAP

T1 - The role of DNMT3B mutations in the pathogenesis of ICF syndrome

AU - Gatto, Sole

AU - D'Esposito, Maurizio

AU - Matarazzo, Maria R.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84949175617&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84949175617&partnerID=8YFLogxK

U2 - 10.1007/978-1-4614-3345-3_2

DO - 10.1007/978-1-4614-3345-3_2

M3 - Chapter

AN - SCOPUS:84949175617

SN - 9781461433453

SN - 1461433444

SN - 9781461433446

VL - 9781461433453

SP - 15

EP - 41

BT - Patho-Epigenetics of Disease

PB - Springer New York

ER -