An upstream initiator-like element suppresses transcription of the rat luteinizing hormone receptor gene.
Expression of the rat LH receptor (rLHR) is characterized by a dynamic response to a variety of hormonal stimuli. In addition to activation, the pattern of rLHR expression is also modulated by repression. In this report, an upstream initiator-like element (UInr-lE), CTCACTCTAA, of which the CTC direct repeat motif (CTCACTC) is conserved in the rat, mouse, and human, was identified as a suppressor element. Disruption of the element resulted in a 2-fold enhancement of promoter activity in the LHR-expressing murine Leydig tumor cells. The sequences of the two major initiators (Inr), Inr3 and Inr4, of the rLHR core promoter are similar to UInr-lE and competed efficiently with UInr-lE in the formation of specific protein complexes, suggesting that the same proteins interact with both UInr-lE and the Inrs in vivo. The Inrs are necessary for full promoter activity because a mutant promoter lacking Inrs showed a 70% reduction in activity. UInr-lE also further suppressed the activity of a mutant promoter lacking Inrs. UInr-lE interacted with transcription factor II-I (TFII-I) and an unidentified nuclear protein. However, dominant-negative inhibition experiments using p70 indicated that TFII-I positively regulates LHR promoter activity through UInr-lE and Inrs, suggesting that TFII-I can compromise the suppression of promoter activity mediated by UInr-lE. UInr-lE also showed binding properties distinct from that of the upstream initiator-like suppressor element (upstream regulatory element: CACTCTCC) of rat and human dynorphin promoters. Transfection assays using mutated promoters indicate that the suppression of rLHR promoter activity could be regulated via specific interactions between UInr-lE and trans-acting factors.
Youn
HyeSook
H
Department of Biotechnology and Biomedical Science, Inje University, Gimhae 61-749, Korea.
Koo
YongBum
Y
Ji
Inhae
I
Ji
Tae H
TH
D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D051381:Rats; D019473:Transcription Factors, TFII / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D019473:Transcription Factors, TFII; D007986:Luteinizing Hormone; D004247:DNA