Disease relevance of MYT1

• Myelin transcription factor 1 (MyT1) immunoreactivity in infants with periventricular leukomalacia [1].
• In the present study, biopsy specimens from human brain tumors were analyzed for expression of Myelin Transcription Factor 1 (MYT1) to explore the extent to which glioma cells reflect characteristic expression of MYT1 in developing glial progenitor cells [2].
• Immunostaining with an antibody against MYT1 revealed widespread immunoreactivity that was most prominent in high-grade oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas as well as in a dysembryoplastic neuroepithelial tumor [2].
• Together, these findings demonstrate that the PlGF gene is responsive to hypoxia and that this response is mediated by MTF-1 [3].
• Our results suggested that MTF-1 was activated during endotoxemia [4].

High impact information on MYT1

• MTF-1 contains six zinc fingers and separate transcriptional activation domains with high contents of acidic and proline residues [5].
• Bioinformatic promoter analyses indicate that both SNPs lead to a gain/loss of putative binding sites for three transcription factors, serum response factor, myelin transcription factor-1, and High Mobility Group Box Protein-1 [6].
• The DNA-binding activity of the Zn finger protein metal response element-binding transcription factor 1 (MTF-1) was rapidly induced both in vivo in mouse Hepa cells, canine MDCK, and human HeLa cells after incubation in medium containing zinc and in vitro in whole-cell extracts to which zinc was added [7].
• These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites [8].
• Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement [8].

Biological context of MYT1

• The MYT1 gene maps to human chromosome 20, while MYT1L maps to a region of human chromosome 2 [9].
• Both zinc finger proteins are found in neurons at early stages of differentiation, with germinal zone cells displaying intense staining for MyT1 [9].
• Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters [8].
• MYT1 immunoreactivity in tumor regions generally correlated with the prevalence of cells exhibiting nuclear immunolabeling with an antibody against Ki-67, suggesting an association of MYT1 with cell proliferation that was also observed in normal adult human and rat brain in the germinal subependymal zone [2].
• In contrast, Myt1 downregulation also abrogated Adriamycin trade mark -induced G(2) arrest but did not cause substantial apoptosis [10].

Anatomical context of MYT1

• 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 [9].
• In the intact human brain, platelet-derived growth factor receptor alpha (PDGF alpha R) and myelin transcription factor 1 (MyTI) transcripts are expressed in 1-2% of cells of the oligodendrocyte lineage (OL), and clusters of such cells can be found in the periventricular region [11].
• Therefore, MyT1 may play an important role in the myelin repair in PVL regions [1].
• The expression of MyT1 immunoreactivity shifted from the nucleus to the cytoplasm of the glial cells in the developmental time course [1].
• Reduction in Wee1, Chk1, or Myt1 levels did not sensitize normal human mammary epithelial cells (HMEC) cells to Adriamycin trade mark -induced apoptosis unlike the situation in Hela cells [10].

Associations of MYT1 with chemical compounds

• It was also noted that zinc-activated recombinant MTF-1 was protected from cadmium only when bound to DNA [12].
• The human metalloregulatory transcription factor, metal-response element (MRE)-binding transcription factor-1 (MTF-1), contains six TFIIIA-type Cys(2)-His(2) motifs, each of which was projected to form well-structured betabetaalpha domains upon Zn(II) binding [13].
• MTF-1 binds to DNA sequence motifs known as metal response elements (MREs) with a core consensus TGCRCNC [14].
• Northern blotting showed that Cd, CHX, or Cd + CHX does not affect the expression of the mRNA of MTF-1 [15].
• Exposing mouse lung endothelial cells (MLEC) to ZnCl(2) or the NO donor, S-Nitroso-N-acetylpenicillamine (SNAP, 200 microM), caused nuclear translocation of a reporter molecule consisting of enhanced green fluorescent protein (EGFP) fused to MTF-1 (pEGFP-MTF-1) [16].

Physical interactions of MYT1

• These data suggest that transition metals, other than zinc, that activate MT gene expression may do so by mechanisms independent of an increase in the DNA binding activity of MTF-1 [12].

Other interactions of MYT1

• In the chronic stage of PVL, MyT1-positive cells were significantly increased around necrotic foci and some of the regions were coincident with increasing MBP and PLP immunoreactivity [1].
• Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis [8].
• Our study reveals distinct roles for Chk1, Wee1, and Myt1 in G(2) checkpoint regulation [10].
• In combination with histopathological studies and analysis of Ki-67 immunoreactivity, examination of MYT1 immunolabeling may provide additional information to aid in the detection and diagnosis of CNS tumors [2].
• High-grade human brain tumors exhibit increased expression of myelin transcription factor 1 (MYT1), a zinc finger DNA-binding protein [2].

Analytical, diagnostic and therapeutic context of MYT1

• MyT1-positive glial cells were first detected at 19 gestational weeks (GWs) and then gradually increased until 26-29 GWs in the control group [1].
• Electrophoretic mobility shift assays detected a specific protein-DNA complex containing MTF-1 in nuclear extracts from hypoxic cells [17].
• RT-PCR results show the maternal expression of MTF-1 transcripts [18].
• The pattern of MTF-1 gene expression during embryonic and early larval development was studied by whole-mount in situ hybridization using DIG-labeled anti-sense RNA probe [18].
• Immunoblotting using antibodies specific for MTF-1 demonstrated that Cd induces a down-regulation of the MTF-1 protein, whereas cotreatment with Cd and CHX blocked the Cd-induced degradation of MTF-1 [15].

References