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. 2010 Dec 27;16(1):89–100. doi: 10.2478/s11658-010-0041-1

ZFAT is a critical molecule for cell survival in mouse embryonic fibroblasts

Keiko Doi 1,2, Takahiro Fujimoto 1,2, Midori Koyanagi 1,2, Toshiyuki Tsunoda 1,2, Yoko Tanaka 1,2, Yasuhiro Yoshida 1, Yasuo Takashima 2, Masahide Kuroki 2, Takehiko Sasazuki 3, Senji Shirasawa 1,2,✉
PMCID: PMC6275631  PMID: 21225468

Abstract

ZFAT was originally identified as an immune-related transcriptional regulator containing 18 C2H2-type zinc-finger domains and one AT-hook. ZFAT is highly conserved among species and functions as an anti-apoptotic molecule in the lymphoblastic leukemia cell line, MOLT-4. We recently demonstrated that ZFAT is an essential molecule for hematopoietic differentiation in blood islands through the direct regulation of particular transcriptional factors, including Tal1, for endothelial cell assembly, and for the branch point formation of capillary-like structures. However, the molecular mechanisms underlying the anti-apoptotic function of ZFAT remain unknown. Here, we report that ZFAT knockdown by small interfering RNA induced apoptosis in mouse embryonic fibroblasts (MEFs). This response had been similarly observed for MOLT-4 cells. To explore the molecular mechanisms for ZFAT in anti-apoptotic function in both MEFs and MOLT-4 cells, microarray expression analysis and quantitative RT-PCR were done. Of interest was that Bcl-2 and Il6st were identified as commonly down-regulated genes by the depletion of ZFAT for both MEFs and MOLT-4 cells. These results suggest that ZFAT is a critical molecule for cell survival in MEFs and MOLT-4 cells at least in part through the regulation of the apoptosis involved in the BCL-2- and IL6st-mediated pathways. Further elucidation of the molecular functions for ZFAT might shed light on the cellular programs in the mesoderm-derived cells.

Electronic Supplementary Material

Supplementary material is available for this article at 10.2478/s11658-010-0041-1 and is accessible for authorized users.

Key words: ZFAT, Transcription factor, MEFs, Apoptosis, Gene expression

Full Text

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Abbreviations used

C2H2

Cys2-His2

ZFAT

zinc-finger gene in autoimmune thyroid disease susceptibility region

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