A Novel Transcriptional Repressor, Rhit, Is Involved in Heat-Inducible and Age-Dependent Expression of Mpv17-Like Protein, a Participant in Reactive Oxygen Species Metabolism
Copyright policy )A Novel Transcriptional Repressor, Rhit, Is Involved in Heat-Inducible and Age-Dependent Expression of Mpv17-Like Protein, a Participant in Reactive Oxygen Species Metabolism
Mpv17-like protein (M-LP) is a protein that has been suggested to be involved in the metabolism of reactive oxygen species. The two M-LP isoforms in mouse, M-LP(S) and M-LP(L), are generated by the alternative usage of promoters. M-LP(S) is expressed exclusively in kidneys after the age of 6 weeks, whereas M-LP(L) is expressed ubiquitously. To elucidate the molecular basis of M-LP(S) expression, we searched for cis-regulatory elements in the promoter region of M-LP(S) and identified heat shock element half-sites as positive elements and a Tramtrack 69K (Ttk 69K) binding site as a negative element. Furthermore, we isolated a novel transcription repressor, Rhit (regulator of heat-induced transcription), that binds to the Ttk 69K binding site within the M-LP(S) promoter by DNA affinity chromatography and confirmed its participation in the transcriptional regulation of M-LP(S) by RNA interference (RNAi). Sequence analysis revealed that Rhit contains a KRAB (Krüppel-associated box) domain and a DNA-binding domain composed of eight C(2)H(2)-type zinc fingers. Interestingly, exposure to heat shock stress resulted in the upregulation of M-LP(S) expression concurrent with the downregulation of Rhit expression. Moreover, the age-dependent expression of M-LP(S) was inversely correlated with that of Rhit. These observations strongly suggest that Rhit acts as a repressor in the heat-induced and age-dependent transcriptional regulation of M-LP(S).
- University of Fukui Japan
Aging, Hot Temperature, Base Sequence, Transcription, Genetic, Molecular Sequence Data, Membrane Proteins, Regulatory Sequences, Nucleic Acid, Cell Line, Repressor Proteins, Mice, Gene Expression Regulation, Mutagenesis, Site-Directed, Animals, Protein Isoforms, Amino Acid Sequence, RNA, Small Interfering, Promoter Regions, Genetic, Reactive Oxygen Species
Aging, Hot Temperature, Base Sequence, Transcription, Genetic, Molecular Sequence Data, Membrane Proteins, Regulatory Sequences, Nucleic Acid, Cell Line, Repressor Proteins, Mice, Gene Expression Regulation, Mutagenesis, Site-Directed, Animals, Protein Isoforms, Amino Acid Sequence, RNA, Small Interfering, Promoter Regions, Genetic, Reactive Oxygen Species
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