Zinc finger artificial transcription factor-based nearest inactive analogue/nearest active analogue strategy used for the identification of plant genes controlling homologous recombination

Abstract Background SOX2 is a transcription factor that is fundamental for early development and for the maintenance of stem cells in multiple adult tissues and also plays an important role in squamous cell differentiation. Amplification of chromosome 3q26 is the most common of the genetic alterations found in squamous cell carcinoma (SCC). SOX2 is a candidate oncogene present in this locus and amplification of SOX2 has been reported in lung and esophageal squamous cell SCC. In this study, we have developed a zinc finger-based artificial transcription factor (ATF) to selectively suppress SOX2 expression in cancer cells and termed the system ATF/SOX2. Methods We engineered the ATF using six zinc finger arrays designed to target a 19 bp site in the SOX2 distal promoter and a KOX transcriptional repressor domain. A recombinant adenoviral vector Ad-ATF/SOX2 that expresses ATF/SOX2 suppressed SOX2 at the mRNA and protein levels in esophageal SCC cells(TE1 and TE4) expressing SOX2. Results Ad-ATF/SOX2 decreased esophageal SCC cells proliferation and colony formation more effectively than the recombinant adenoviral vector Ad-shSOX2, which expresses SOX2 short hairpin RNA (shSOX2). Ad-ATF/SOX2 induced the cell cycle inhibitor CDKN1A more strongly than Ad-shSOX2. Moreover, Ad-ATF/SOX2 effectively inhibited tumor growth in a SCC xenograft mouse model. Conclusion In this study, we have shown that the targeted down-regulation of SOX2 using ATF based technologies can be used as an effective tool for the treatment of SCC in esophageal cancers that express SOX2. Our results indicate that ATF/SOX2 would lead to the development of an effective molecular-targeted therapy for esophageal SCC. Disclosure All authors have declared no conflicts of interest.

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Faculty Opinions recommendation of Divergent roles of a pair of homologous jumonji/zinc-finger-class transcription factor proteins in the regulation of Arabidopsis flowering time.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1021671.247641 ◽

2004 ◽

Author(s):

José Luis Riechmann

Keyword(s):

Transcription Factor ◽

Flowering Time ◽

Zinc Finger ◽

Transcription Factor Proteins

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Faculty Opinions recommendation of The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1024248.290751 ◽

2005 ◽

Author(s):

Kyoko Hayakawa

Keyword(s):

Transcription Factor ◽

T Cell ◽

Zinc Finger ◽

Cell Lineage ◽

Cd8 T Cell ◽

Lineage Commitment ◽

Zinc Finger Transcription Factor

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Faculty Opinions recommendation of Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718215429.793489962 ◽

2014 ◽

Author(s):

Robert K Herman

Keyword(s):

Transcription Factor ◽

Caenorhabditis Elegans ◽

Zinc Finger ◽

Zinc Finger Transcription Factor

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Faculty Opinions recommendation of Regulation of Aluminum Resistance in Arabidopsis Involves the SUMOylation of the Zinc Finger Transcription Factor STOP1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738884406.793579957 ◽

2020 ◽

Author(s):

Ramón Serrano

Keyword(s):

Transcription Factor ◽

Zinc Finger ◽

Zinc Finger Transcription Factor ◽

Aluminum Resistance

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The apple C2H2-type zinc finger transcription factor MdZAT10 positively regulates JA-induced leaf senescence by interacting with MdBT2

Horticulture Research ◽

10.1038/s41438-021-00593-0 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Kuo Yang ◽

Jian-Ping An ◽

Chong-Yang Li ◽

Xue-Na Shen ◽

Ya-Jing Liu ◽

...

Keyword(s):

Mass Spectrometry ◽

Transcription Factor ◽

Liquid Chromatography ◽

Zinc Finger ◽

Leaf Senescence ◽

Transcriptional Activity ◽

Molecular Mechanisms ◽

Liquid Chromatography Mass Spectrometry ◽

Zinc Finger Transcription Factor ◽

Insight Into

AbstractJasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.

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