title: The major histocompatibility complex class II Ea promoter requires TFIID binding to an initiator sequence.
abstract: The major histocompatibility complex (MHC) class II Ea promoter is dependent on the presence of conserved upstream X and Y boxes and of initiator (Inr) sequences. In vitro transcription analysis of the Inr region with linker-scanning mutants pinpoints a functionally essential element that shows homology to the terminal deoxynucleotidyltransferase (TdT) Inr; contrary to the TdT Inr and other Inrs identified so far, the key sequence, between positions +5 and +12, is located within a transcribed area. Swapping the TdT sequence into the corresponding Ea position leads to a fivefold increase in transcription rate, without altering start site selection. Inr-binding proteins LBP-1/CP2 and TIP--a TdT Inr-binding protein unrelated to YY1--recognize the Ea Inr; they interact with overlapping yet distinct sequences around the Cap site, but their binding does not coincide with Ea Inr activity. A good correlation is, rather, found with binding of immunopurified holo-TFIID to this element. TFIID interacts both with Ea TATA-like and Inr sequences, but only the latter is functionally relevant. Unlike TBP, TFIID binds in the absence of TFIIA, indicating a stabilizing role for TBP-associated factors in Ea promoter recognition. Sequence comparison with other mouse and human MHC class II promoters suggests a common mechanism of start site(s) selection for the MHC class II gene family.
authors.affiliation: Dipartimento di Genetica e Biologia dei Microrganismi, Università di Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bellorini
authors.forename: J C
authors.initials: JC
authors.lastname: Dantonel
authors.forename: J B
authors.initials: JB
authors.lastname: Yoon
authors.forename: R G
authors.initials: RG
authors.lastname: Roeder
authors.forename: L
authors.initials: L
authors.lastname: Tora
authors.forename: R
authors.initials: R
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D005802:Genes, MHC Class II; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D035362:Transcription Factor TFIID; D014157:Transcription Factors; C085968:UBP1 protein, human; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2