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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8465848 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tauchmannsamantha nsd1alysinemethyltransferasebetweendevelopmentaldisordersandcancer AT schwallerjuerg nsd1alysinemethyltransferasebetweendevelopmentaldisordersandcancer |