Three functional classes of transcriptional activation domain.
We have studied the abilities of different transactivation domains to stimulate the initiation and elongation (postinitiation) steps of RNA polymerase II transcription in vivo. Nuclear run-on and RNase protection analyses revealed three classes of activation domains: Sp1 and CTF stimulated initiation (type I); human immunodeficiency virus type 1 Tat fused to a DNA binding domain stimulated predominantly elongation (type IIA); and VP16, p53, and E2F1 stimulated both initiation and elongation (type IIB). A quadruple point mutation of VP16 converted it from a type IIB to a type I activator. Type I and type IIA activators synergized with one another but not with type IIB activators. This observation implies that synergy can result from the concerted action of factors stimulating two different steps in transcription: initiation and elongation. The functional differences between activators may be explained by the different contacts they make with general transcription factors. In support of this idea, we found a correlation between the abilities of activators, including Tat, to stimulate elongation and their abilities to bind TFIIH.
Blau
J
J
Molecular Genetics of Differentiation Laboratory, Imperial Cancer Research Fund, London, UK.
Xiao
H
H
McCracken
S
S
O'Hare
P
P
Greenblatt
J
J
Bentley
D
D
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D012319:RNA Polymerase II / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012260:Ribonucleases; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D015696:Gene Products, tat; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D015500:Chloramphenicol O-Acetyltransferase; D012319:RNA Polymerase II; D012260:Ribonucleases