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NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer

Recurrent epigenomic alterations associated with multiple human pathologies have increased the interest in the nuclear receptor binding SET domain protein 1 (NSD1) lysine methyltransferase. Here, we review the current knowledge about the biochemistry, cellular function and role of NSD1 in human dise...

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Autores principales: Tauchmann, Samantha, Schwaller, Juerg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465848/
https://www.ncbi.nlm.nih.gov/pubmed/34575025
http://dx.doi.org/10.3390/life11090877
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author Tauchmann, Samantha
Schwaller, Juerg
author_facet Tauchmann, Samantha
Schwaller, Juerg
author_sort Tauchmann, Samantha
collection PubMed
description Recurrent epigenomic alterations associated with multiple human pathologies have increased the interest in the nuclear receptor binding SET domain protein 1 (NSD1) lysine methyltransferase. Here, we review the current knowledge about the biochemistry, cellular function and role of NSD1 in human diseases. Several studies have shown that NSD1 controls gene expression by methylation of lysine 36 of histone 3 (H3K36me1/2) in a complex crosstalk with de novo DNA methylation. Inactivation in flies and mice revealed that NSD1 is essential for normal development and that it regulates multiple cell type-specific functions by interfering with transcriptional master regulators. In humans, putative loss of function NSD1 mutations characterize developmental syndromes, such as SOTOS, as well as cancer from different organs. In pediatric hematological malignancies, a recurrent chromosomal translocation forms a NUP98-NSD1 fusion with SET-dependent leukemogenic activity, which seems targetable by small molecule inhibitors. To treat or prevent diseases driven by aberrant NSD1 activity, future research will need to pinpoint the mechanistic correlation between the NSD1 gene dosage and/or mutational status with development, homeostasis, and malignant transformation.
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spelling pubmed-84658482021-09-27 NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer Tauchmann, Samantha Schwaller, Juerg Life (Basel) Review Recurrent epigenomic alterations associated with multiple human pathologies have increased the interest in the nuclear receptor binding SET domain protein 1 (NSD1) lysine methyltransferase. Here, we review the current knowledge about the biochemistry, cellular function and role of NSD1 in human diseases. Several studies have shown that NSD1 controls gene expression by methylation of lysine 36 of histone 3 (H3K36me1/2) in a complex crosstalk with de novo DNA methylation. Inactivation in flies and mice revealed that NSD1 is essential for normal development and that it regulates multiple cell type-specific functions by interfering with transcriptional master regulators. In humans, putative loss of function NSD1 mutations characterize developmental syndromes, such as SOTOS, as well as cancer from different organs. In pediatric hematological malignancies, a recurrent chromosomal translocation forms a NUP98-NSD1 fusion with SET-dependent leukemogenic activity, which seems targetable by small molecule inhibitors. To treat or prevent diseases driven by aberrant NSD1 activity, future research will need to pinpoint the mechanistic correlation between the NSD1 gene dosage and/or mutational status with development, homeostasis, and malignant transformation. MDPI 2021-08-25 /pmc/articles/PMC8465848/ /pubmed/34575025 http://dx.doi.org/10.3390/life11090877 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tauchmann, Samantha
Schwaller, Juerg
NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title_full NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title_fullStr NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title_full_unstemmed NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title_short NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer
title_sort nsd1: a lysine methyltransferase between developmental disorders and cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465848/
https://www.ncbi.nlm.nih.gov/pubmed/34575025
http://dx.doi.org/10.3390/life11090877
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