Open AccessA Novel Transcriptional Repressor, Rhit, Is Involved in Heat-Inducible and Age-Dependent Expression of Mpv17-Like Protein, a Participant in Reactive Oxygen Species Metabolism
Author(s) -
Reiko Iida,
Misuzu Ueki,
Toshihiro Yasuda
Publication year - 2010
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01025-09
Subject(s) - repressor , biology , microbiology and biotechnology , promoter , transcription (linguistics) , transcriptional regulation , transcription factor , heat shock protein , zinc finger , downregulation and upregulation , gene expression , regulation of gene expression , gene , biochemistry , linguistics , philosophy
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-LPS and M-LPL , are generated by the alternative usage of promoters. M-LPS is expressed exclusively in kidneys after the age of 6 weeks, whereas M-LPL is expressed ubiquitously. To elucidate the molecular basis of M-LPS expression, we searched forcis -regulatory elements in the promoter region of M-LPS 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-LPS promoter by DNA affinity chromatography and confirmed its participation in the transcriptional regulation of M-LPS by RNA interference (RNAi). Sequence analysis revealed that Rhit contains a KRAB (Krüppel-associated box) domain and a DNA-binding domain composed of eight C2 H2 -type zinc fingers. Interestingly, exposure to heat shock stress resulted in the upregulation of M-LPS expression concurrent with the downregulation of Rhit expression. Moreover, the age-dependent expression of M-LPS 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-LPS .