This page was published for Genetics 564 at the University of Wisconsin- Madison
Overview of the Histone-Lysine N-Methyltransferase, H3 Lysine-36 and H4 Lysine-20 Specific isoform b (NSD1)
The key gene in Sotos syndrome, NSD1, encodes a 2696 amino acid protein called histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific isoform b, or more generally known as NSD1 (Figure 1). Although exact cellular localization is unknown, NSD1 is generally found in the nucleus amongst the chromosomes [1]. This is where the histone methyltransferase function of the protein takes place. NSD1 acts to catalyze the methylation, or silencing, of lysines 36 and 20 in histones H3 and H4, respectively. Methylations of histones are post-transcriptional epigenetic modifications that usually result in gene silencing; however, depending on cellular context, methylations may act positively or negatively on transcriptional regulation [2].
Figure 1: This is the crystalline structure of NSD1.
Protein domains
The lack of fundamental knowledge on the exact localization and overarching function of the gene is partially due to the existence of so many domains. Major domains include PHD domains, which are chromatin associated zinc fingers; PWWP, a chromatin associated domain, SET, a protein lysine methyltransferase enzyme that helps to mediate protein-protein interaction; RING, a protein interaction mediator; and pre/postSET domains for stabilization. For more information about these domains, please refer to Domains & Motifs [3].
Localization
As previously stated, exact localization of NSD1 is unknown. However, using Gene Ontology, a consensus can be reached that generally, NSD1 can be found in the nucleus amongst the chromosomes. Cell types containing NSD1 include the brain, kidney, skeletal muscle, spleen, thymus, and faintly in the lung [4].
References:
[1] The Gene Cards Human Gene Database. (2014). Weizmann Institute of Science. Retrieved March 2, 2014, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=NSD1
[2] Trievel, R. C. (2004). Structure and function of histone methyltransferases. Crit Rev Eukaryot Gene Expr, 14(3), 147-169.
[3] Carpenter, P. B. (2014). Description of Research. Epigenetics and the NSD family in development and disease. Retrieved March 5, 2014, 2014
[4] Kurotaki, N., Harada, N., Yoshiura, K.-i., Sugano, S., Niikawa, N., & Matsumoto, N. (2001). Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Gene, 279(2), 197-204. doi: http://dx.doi.org/10.1016/S0378-1119(01)00750-8
[1] The Gene Cards Human Gene Database. (2014). Weizmann Institute of Science. Retrieved March 2, 2014, from http://www.genecards.org/cgi-bin/carddisp.pl?gene=NSD1
[2] Trievel, R. C. (2004). Structure and function of histone methyltransferases. Crit Rev Eukaryot Gene Expr, 14(3), 147-169.
[3] Carpenter, P. B. (2014). Description of Research. Epigenetics and the NSD family in development and disease. Retrieved March 5, 2014, 2014
[4] Kurotaki, N., Harada, N., Yoshiura, K.-i., Sugano, S., Niikawa, N., & Matsumoto, N. (2001). Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Gene, 279(2), 197-204. doi: http://dx.doi.org/10.1016/S0378-1119(01)00750-8