TY - JOUR
T1 - In vivo evaluation of GG2–GG1/A2 element activity in the insulin promoter region using the CRISPR–Cas9 system
AU - Noguchi, Hirofumi
AU - Miyagi-Shiohira, Chika
AU - Kinjo, Takao
AU - Saitoh, Issei
AU - Watanabe, Masami
N1 - Funding Information:
This work was supported in part by JSPS KAKENHI Grant Numbers JP20H03745, JP19K09051, and Okinawa Science and Technology Innovation System Construction Project.
Funding Information:
We thank Naomi Kakazu (University of the Ryukyus) for the office processing and Yuki Kawahira, Ikue Honda (University of the Ryukyus), Seiya Mizuno, Yoko Tanimoto, Satoru Takahashi, and Fumihiro Sugiyama (University of Tsukuba) for technical support. This work was supported in part by JSPS KAKENHI Grant Numbers JP20H03745, JP19K09051, and Okinawa Science and Technology Innovation System Construction Project.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - The insulin promoter is regulated by ubiquitous as well as pancreatic β-cell-specific transcription factors. In the insulin promoter, GG2–GG1/A2–C1 (bases − 149 to − 116 in the human insulin promoter) play important roles in regulating β-cell-specific expression of the insulin gene. However, these events were identified through in vitro studies, and we are unaware of comparable in vivo studies. In this study, we evaluated the activity of GG2–GG1/A2 elements in the insulin promoter region in vivo. We generated homozygous mice with mutations in the GG2–GG1/A2 elements in each of the Ins1 and Ins2 promoters by CRISPR–Cas9 technology. The mice with homozygous mutations in the GG2–GG1/A2 elements in both Ins1 and Ins2 were diabetic. These data suggest that the GG2–GG1/A2 element in mice is important for Ins transcription in vivo.
AB - The insulin promoter is regulated by ubiquitous as well as pancreatic β-cell-specific transcription factors. In the insulin promoter, GG2–GG1/A2–C1 (bases − 149 to − 116 in the human insulin promoter) play important roles in regulating β-cell-specific expression of the insulin gene. However, these events were identified through in vitro studies, and we are unaware of comparable in vivo studies. In this study, we evaluated the activity of GG2–GG1/A2 elements in the insulin promoter region in vivo. We generated homozygous mice with mutations in the GG2–GG1/A2 elements in each of the Ins1 and Ins2 promoters by CRISPR–Cas9 technology. The mice with homozygous mutations in the GG2–GG1/A2 elements in both Ins1 and Ins2 were diabetic. These data suggest that the GG2–GG1/A2 element in mice is important for Ins transcription in vivo.
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U2 - 10.1038/s41598-021-99808-6
DO - 10.1038/s41598-021-99808-6
M3 - Article
C2 - 34645928
AN - SCOPUS:85117391023
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 20290
ER -
