Induction of long interspersed nucleotide element-1 (L1) retrotransposition by 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct.
Long interspersed nucleotide element-1 (L1) is a retroelement comprising about 17% of the human genome, of which 80-100 copies are competent as mobile elements (retrotransposition: L1-RTP). Although the genetic structures modified during L1-RTP have been clarified, little is known about the cellular signaling cascades involved. Herein we found that 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct postulated as a candidate physiological ligand of the aryl hydrocarbon receptor (AhR), induces L1-RTP. Notably, RNA-interference experiments combined with back-transfection of siRNA-resistant cDNAs revealed that the induction of L1-RTP by FICZ is dependent on AhR nuclear translocator-1 (ARNT1), a binding partner of AhR, and the activation of cAMP-responsive element-binding protein. However, our extensive analyses suggested that AhR is not required for L1-RTP. FICZ stimulated the interaction of the L1-encoded open reading frame-1 (ORF1) and ARNT1, and recruited ORF1 to chromatin in a manner dependent on the activation of mitogen-activated protein kinase. Along with our additional observations that the cellular cascades for FICZ-induced L1-RTP were different from those of L1-RTP triggered by DNA damage, we propose that the presence of the cellular machinery of ARNT1 mediates L1-RTP. A possible role of ARNT1-mediated L1-RTP in the adaptation of living organisms to environmental changes is discussed.
Okudaira
Noriyuki
N
National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.
Iijima
Kenta
K
Koyama
Takayoshi
T
Minemoto
Yuzuru
Y
Kano
Shigeyuki
S
Mimori
Akio
A
Ishizaka
Yukihito
Y
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D001483:Base Sequence; D002227:Carbazoles / Q000494:pharmacology* / Q000528:radiation effects; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects*; D020935:MAP Kinase Signaling System; D010782:Photolysis; D011506:Proteins / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D014364:Tryptophan / Q000528:radiation effects; D014466:Ultraviolet Rays
C111855:6-formylindolo(3,2-b)carbazole; C497396:ARNT protein, human; C115163:CREB1 protein, human; D002227:Carbazoles; D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D008024:Ligands; C531245:ORF1 protein, human; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D014364:Tryptophan