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ID 40618
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title alternative
Kruppel様ジンクフィンガー型転写因子であるGLI-similar 1は低酸素誘導性転写因子の非古典的機構によって制御されている
creator
Elham, Khalesi
subject
GLIS1
Hypoxia
HIF
AP1
Gene transcription
NDC
Medical sciences
abstract
GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression remain unclear. We have therefore examined GLIS1 expression in various cancer cell lines and demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions. Importantly, GLIS1 expression was significantly attenuated in VHL-overexpressing renal cell carcinoma cells compared to the VHL-deficient parent control. Moreover, promoter analysis demonstrated that GLIS1 transcription was regulated by hypoxia through a hypoxia-inducible factors (HIFs)-dependent mechanism. Co-transfection experiments revealed that HIF-2a had greater potency on the GLIS1 promoter activation than HIF-1a. Subsequent studies using wild-type and mutant HIF-2a demonstrated that DNA binding activity was not necessary but TADs were critical for GLIS1 induction. Finally, co-transfection experiments indicated that HIF-2a cooperated with AP-1 family members in upregulating GLIS1 transcription. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation.
language
eng
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
relation references
Elham Khalesi, Hideaki Nakamura, Kian Leong Lee, Andika Chandra Putra, Takahiro Fukazawa, Yumi Kawahara, Yuichi Makino, Lorenz Poellinger, Louis Yuge and Keiji Tanimoto; The Kruppel-like zinc finger transcription factor, GLI-similar 1, is regulated by hypoxia-inducible factors via non-canonical mechanisms.; Biochemical and Biophysical Research Communications, Volume 441, Issue 2, 15 November 2013, Pages 499-506 (DOI: 10.1016/j.bbrc.2013.10.083)
relation references URL
http://doi.org/10.1016/j.bbrc.2013.10.083
grantid
甲第6373号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(保健学)
degreename En
Philosophy in Health Science
degreelevel
doctoral
date of granted
2014-03-23
department
Graduate School of Health Science