Alternative titles; symbols
HGNC Approved Gene Symbol: MYT1
Cytogenetic location: 20q13.33 Genomic coordinates (GRCh38) : 20:64,164,452-64,242,253 (from NCBI)
MYT1 is a C2HC-type zinc finger transcription factor that is highly expressed in developing neural tissues, as well as in developing pancreas (Wang et al., 2007).
Kim and Hudson (1992) cloned a partial cDNA encoding MYT1, which they called PLPB1, from a human fetal brain cDNA library. The deduced 726-amino acid sequence has 2 tandem zinc fingers and 4 tandem zinc fingers separated by a 316-amino acid region containing acidic and serine-rich domains. The sequence also has numerous potential phosphorylation sites. Northern blot analysis detected highest expression of a major 5.5-kb MYT1 transcript in embryonic day-15 mouse brain and in 8-month-old human brain. Lower expression was detected in adult mouse and human brain, and no expression was detected in other tissues. Gel shift analysis indicated that MYT1 was expressed predominantly in the nervous system and in glial cell lines.
Kim et al. (1997) cloned full-length mouse Myt1. The transcript contains RNA instability elements in its 3-prime UTR. The deduced 1,077-amino acid protein contains clusters of 2 zinc fingers and 4 zinc fingers separated by 289 amino acids. Northern blot analysis of developing rat brain detected Myt1 expression from embryonic day 13, with a peak at embryonic days 15 to 17. Expression then declined and was maintained at very low levels in adult. Northern blot analysis detected highest Myt1 expression in cultured rat oligodendrocyte progenitor cells, with little to no expression in cultured astrocytes or oligodendrocytes. In situ hybridization of postnatal day-3 cervical spinal cord revealed a pattern of Myt1 expression consistent with glial cells.
Wang et al. (2007) stated that mouse Myt1 is expressed as 2 splice variants that differ in their 5-prime ends. Immunohistochemical analysis detected mouse Myt1 expression in pancreatic endocrine cells during embryonic development. The percentage of insulin (INS; 176730)-positive cells that expressed Myt1 decreased with age.
Lopez et al. (2016) identified 2 zebrafish genes, myt1a and myt1b, as homologs of human MYT1. Spatiotemporal expression studies showed that myt1a was significantly expressed throughout embryogenesis, whereas myt1b expression was only slightly detected from 36 hours postfertilization (hpf). In adult tissues, both genes were mainly expressed in brain and ovaries and myt1a was also expressed in testis. By whole-mount in situ hybridization, myt1a transcripts were first detected at 10 somites in the midbrain-hindbrain boundary, and at 48 hpf in the olfactory bulb, the midbrain-hindbrain boundary, and the hindbrain; myt1b expression was not detected.
By PCR of a panel of human/rodent cell lines, Kim et al. (1997) mapped the MYT1 gene to chromosome 20. They mapped the mouse Myt1 gene to a region of chromosome 2 that shares homology of synteny with human chromosome 20q13.
Gross (2016) mapped the MYT1 gene to chromosome 20q13.33 based on an alignment of the MYT1 sequence (GenBank BC062313) with the genomic sequence (GRCh38).
Using gel mobility shift assays, Kim and Hudson (1992) demonstrated that recombinant MYT1 fragments containing either the upstream 2 zinc fingers or the downstream 4 zinc fingers bound the same cis regulatory element in the PLP1 (300401) promoter in vitro. DNA binding required Zn(2+), but not other divalent cations.
By affinity purification in mouse Neuro2a neuroblastoma cells, Yokoyama et al. (2014) identified Myt1 as an Lsd1 (KDM1A; 609132)-interacting protein. Real-time quantitative PCR showed that Myt1 was specifically expressed in mouse brain, and immunostaining showed that Lsd1 and Myt1 formed a protein complex in TuJ1-positive neurons in adult mouse brain. Fractionation analysis revealed that Lsd1 and Myt1 interacted directly to form a stable multiprotein complex containing Corest (RCOR; 607675) and Hdac (see 601241) that the authors named 'neural cell-specific Lsd1 complex' (nLSD1 complex). Myt1 and Lsd1 coregulated neural-specific genes as a protein complex in Neuro2a cells. In particular, the nLSD1 complex controlled cell proliferation by directly targeting Pten (601728) gene expression through epigenetic regulation.
To investigate the relationship between the teratogenic agent retinoic acid and MYT1, Lopez et al. (2016) performed RT-qPCR in HEK293 cells treated with all-trans retinoic acid for 48 hours. They observed a 2.5-fold increase in endogenous MYT1 expression. In addition, overexpression of wildtype MYT1 for 24 hours induced a 1.5-fold downregulation of the retinoic acid receptor RARB (180220).
For discussion of a possible association between variation in the MYT1 gene and hemifacial microsomia, see 164210.
Wang et al. (2007) found that Myt1 -/- mice appeared normal but died immediately upon birth. Diaphragms of Myt1 -/- newborns showed improper innervation, suggesting that Myt1 -/- mice died of respiratory failure. In Myt1 -/- embryonic pancreas, a significant number of endocrine cells coexpressed pancreatic polypeptide (PPY; 167780) with insulin or PPY with somatostatin (SST; 182450) at all stages. Specific inactivation of Myt1 in pancreas, duodenum, and stomach resulted in animals that were viable, fertile, and indistinguishable from wildtype. Again, a significant portion of pancreatic endocrine cells coexpressed PPY with insulin or SST, and a significant number also coexpressed insulin with glucagon (GCG; 138030). Cells coexpressing insulin with PPY or GCG showed genetic markers that suggested immaturity. Tissue-specific Myt1 mutant males developed glucose intolerance with age due to inadequate glucose-stimulated insulin secretion. Embryos with either global or tissue-specific Myt1 deletion showed pancreatic expression of Myt1l (613084) and Myt3 (ST18 617155) mRNA that was not observed in wildtype animals, suggesting a partial compensatory response in Myt1 mutant animals.
Lopez et al. (2016) performed transient knockdown of myt1a in zebrafish and observed 37 to 67% craniofacial cartilage alterations compared to uninjected controls at 5 days postfertilization, including flattening of ceratohyal cartilage, shortened or increased distance between the ceratohyal and Meckel cartilages, abnormal angulation between the ceratohyal and palatoquadrate cartilages, and abnormal angulation between the 2 ceratohyal cartilages. The authors noted that the craniofacial cartilage alterations appeared to be specific, as only a few animals presented extracranial malformations and no difference was observed in the standard length between injected zebrafish and controls. Knockdown of the other zebrafish MYT1 homolog, myt1b, did not induce any morphologic defects, and knockdown of both myt1a and myt1b did not induce any additional features. Attempted rescue of myt1a knockdown by coinjection of wildtype MYT1 cRNA did not statistically decrease the craniofacial cartilage defects, although a tendency was observed. In addition, analysis of the neural crest cell marker sox10 (602229) revealed 3-fold overexpression of sox10 in the myt1a morphants at 10 somites.
Gross, M. B. Personal Communication. Baltimore, Md. 11/3/2016.
Kim, J. G., Armstrong, R. C., Agoston, D., Robinsky, A., Wiese, C., Nagle, J., Hudson, L. D. Myelin transcription factor 1 (Myt1) of the oligodendrocyte lineage, along with a closely related CCHC zinc finger, is expressed in developing neurons in the mammalian central nervous system. J. Neurosci. Res. 50: 272-290, 1997. [PubMed: 9373037] [Full Text: https://doi.org/10.1002/(SICI)1097-4547(19971015)50:2<272::AID-JNR16>3.0.CO;2-A]
Kim, J. G., Hudson, L. D. Novel member of the zinc finger superfamily: a C(2)-HC finger that recognizes a glia-specific gene. Molec. Cell. Biol. 12: 5632-5639, 1992. [PubMed: 1280325] [Full Text: https://doi.org/10.1128/mcb.12.12.5632-5639.1992]
Lopez, E., Berenguer, M., Tingaud-Sequeira, A., Marlin, S., Toutain, A., Denoyelle, F., Picard, A., Charron, S., Mathieu, G., de Belvalet, H., Arveiler, B., Babin, P. J., Lacombe, D., Rooryck, C. Mutations in MYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS. J. Med. Genet. 53: 752-760, 2016. [PubMed: 27358179] [Full Text: https://doi.org/10.1136/jmedgenet-2016-103774]
Wang, S., Zhang, J., Zhao, A., Hipkens, S., Magnuson, M. A., Gu, G. Loss of Myt1 function partially compromises endocrine islet cell differentiation and pancreatic physiological function in the mouse. Mech. Dev. 124: 898-910, 2007. [PubMed: 17928203] [Full Text: https://doi.org/10.1016/j.mod.2007.08.004]
Yokoyama, A., Igarashi, K., Sato, T., Takagi, K., Otsuka I, M., Shishido, Y., Baba, T., Ito, R., Kanno, J., Ohkawa, Y., Morohashi, K., Sugawara, A. Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex. J. Biol. Chem. 289: 18152-18162, 2014. [PubMed: 24828497] [Full Text: https://doi.org/10.1074/jbc.M114.566448]