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A new transcription factor ATG10S activates IFNL2 transcription by binding at an IRF1 site in HepG2 cells
- Source :
- Autophagy
- Publication Year :
- 2020
-
Abstract
- IFNL2 is a potent antiviral interferon, but the regulation of its gene expression is not fully clear. Here, we report the regulation of ATG10S for IFNL2 transcription. Through sequential deletion of the IFNL2 promoter sequence, we found LP1-1, a fragment of the promoter responding to ATG10S activity. Subcellular localization and DNA immunoprecipitation assays showed ATG10S translocating into the nucleus and binding to LP1-1. Online prediction for transcription factor binding sites showed an IRF1 targeting locus in LP1-1. Luciferase assays, RT-PCR, and western blot analysis revealed a core motif (CAAGAC) existing in LP1-1, which determined ATG10S and IRF1 activity; individual nucleotide substitution showed that the functional nucleotides of ATG10S targeting were C1, A3, and C6, and the ones associated with IRF1 were A3 and G4 within the core motif. Co-immunoprecipitation assays revealed ATG10S combination with KPNA1/importin α, KPNB1/importin β, and IRF1. The knockdown of endogenous IRF1 increased ATG10S activity on IFNL2 transcription. These results indicate that ATG10S as a transcription factor competes with IRF1 for the same binding site to promote IFNL2 gene transcription. Abbreviations: ATG10: autophagy related 10; ATG10S: the shorter isoform of autophagy related 10; BD: binding domain; CM: core motif; co-IP: co-immunoprecipitation; GFP: green fluorescent protein; HCV: hepatitis C virus; IF: immunofluorescence; IFN: interferon; IRF: interferon regulatory factor; LP: lambda promoter; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; RLU: relative light unit; SQSTM1: sequestosome 1.
- Subjects :
- 0301 basic medicine
Gene isoform
Transcriptional Activation
Transcription, Genetic
Amino Acid Motifs
Green Fluorescent Proteins
Vesicular Transport Proteins
Autophagy-Related Proteins
Biology
Models, Biological
03 medical and health sciences
Sequestosome 1
Protein Domains
Transcription (biology)
Humans
Protein Isoforms
Binding site
education
Promoter Regions, Genetic
Molecular Biology
Transcription factor
Cell Nucleus
education.field_of_study
Binding Sites
030102 biochemistry & molecular biology
Base Sequence
Interleukins
Cell Biology
Hep G2 Cells
Molecular biology
DNA binding site
Protein Transport
030104 developmental biology
IRF1
Interferon regulatory factors
Interferon Regulatory Factor-1
Protein Binding
Transcription Factors
Research Paper
Subjects
Details
- ISSN :
- 15548635
- Volume :
- 16
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Autophagy
- Accession number :
- edsair.doi.dedup.....93f94201d70846da17c58be5aaa08fd9