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Two different, overlapping pathways of transcription initiation are active on the TATA-less human androgen receptor promoter. The role of Sp1
Ist Teil von
The Journal of biological chemistry, 1993-05, Vol.268 (13), p.9296-9301
Ort / Verlag
United States: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1993
Quelle
MEDLINE
Beschreibungen/Notizen
In this study, the minimal promoter requirements of the TATA-less human androgen receptor (hAR) gene promoter are described.
The hAR promoter is characterized by a short GC-box (-59/-32) and a long homopurine stretch (-117/-60). Two major transcription
initiation sites, AR transcription initiation site I (AR-TIS I, (+1/2/3)) and AR transcription initiation site II (AR-TIS
II, (+12/13)) are located in a 13-base pair region (Faber, P. W., van Rooij, H. C. J., van der Korput, J. A. G. M., Baarends,
W. M., Brinkmann, A. O., Grootegoed, J. A., and Trapman, J. (1991) J. Biol. Chem. 266, 10743-10749). Transient transfection
of COS cells with hAR promoter deletion and mutant constructs, followed by RNA isolation and S1 nuclease protection analysis
showed that the process of transcription initiation through AR-TIS I and AR-TIS II is regulated by different promoter sequences.
The GC-box directed initiation from AR-TIS II but did not affect AR-TIS I utilization, which is dependent upon sequences between
positions -5 and +57. Band shift analysis identified the transcription factor Sp1 as the protein interacting with the GC-box.
A single Sp1 binding sequence was found to be present in the GC-box. Footprint analysis confirmed the interaction of Sp1 with
this sequence. The differential initiation through AR-TIS I and AR-TIS II was substantiated by the introduction of point mutations
in the Sp1 binding sequence: only mutations that specifically abolished Sp1 binding interfered with AR-TIS II utilization,
but all mutations left AR-TIS I initiation intact.