Transcription of a subset of human class II major histocompatibility complex genes is regulated by a nucleoprotein complex that contains c-fos or an antigenically related protein.

Abstract

Transcription of a subset of human class II major histocompatibility complex genes is regulated by a nucleoprotein complex that contains c-fos or an antigenically related protein ( Contributed by Jack L. Strominger, December 20, 1990 ABSTRACT Transcriptional regulation of the human major histocompatibility complex class II genes requires at least two upstream elements, the X and Y boxes, located in the -50-to -150-base-pair region of all class II promoters. The DRA and DPB promoters contain phorbol ester-responsive elements overlapping the 3' side of their X boxes. Mutation of this sequence down-regulates the efficiency of the DRA promoter, suggesting that a positive regulator(s) binds to this site. In this report, anti-sense c-os RNA and an anti-c-fos antibody were used to show that the product of the protooncogene c-fos or an antigenically related protein is a component of a complex that binds to the X box and is required for maximal transcription from the DRA and DPB promoters. As c-fos (or its related proteins) cannot bind alone to DNA, these results suggest that it may dimerize with other members of the JUN/AP-I family, such as hXBP1, to participate in the activation of a subset of class II major histocompatibility complex genes.

High mobility group I/Y protein functions as a specific cofactor for Oct-2A: mapping of interaction domains

“…The pCGOct-2L Ϫ plasmid is the Oct-2 plasmid in which the leucine codons for residues 396 and 403 (in the putative leucine zipper of Oct-2) were mutated to isoleucine codons [8]. The HMG I expression vector and the DRA300CAT plasmid have been described [34,45].…”

“…A ␤-galactosidase expression vector (pSV-␤-gal; Promega) was included to monitor transfection efficiency. Forty eight hours after transfection, the cells were harvested, cell extracts prepared, and assayed for CAT activity as described [34]. CAT activity was quantitated by counting portions of the TLC plate in a liquid scintillation counter.…”

“…In addition to a TATA motif, these include the X, Y, and Z boxes; elements whose sequences as well as stereospecific relationships to each other are highly conserved [16][17][18][19][20][21][22][23][24][25][26]. Several proteins that interact specifically with these cis-acting elements have been described [27][28][29][30][31][32][33][34][35][36][37][38]. A non-DNA binding protein (CIITA) whose expression pattern correlates with class II gene transcription and that strongly transactivates class II genes when expressed in class II-negative cells has also been identified [39,40].…”

A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).

“…The lack of RFXbinding activity in patients from groups B and C also correlates with an abnormal chromatin structure at the MHC class II promoter as judged from the pattern of DNase I hypersensitivity (G6nczy et al 1989), and with an unoccupied MHC class II promoter phenotype in vivo (Kara andGlimcher 1991, 1993). The defect in RFX binding is highly specific and does not concern other MHC class II promoter-binding proteins such as the Y boxbinding protein NF-Y {Hooft van Huijsduijnen et al 1990;Mantovani et al 1992), X2 box-binding proteins such as c-Jun, c-Fos, hXBP1, mXBP, and X2bp (Liou et al 1988(Liou et al , 1990Andersson and Peterlin 1990;Ono et al 1991a, b;Sloan et al 1992;Reith et al 1994a), and several X box-binding proteins that are distinct from RFX (Reith et al , 1994cKouskoff et al 1991;Herrero Sanchez et al 1992). This has led us to suggest that the absence of RFX-binding activity is the molecular defect responsible for MHC class II deficiency in patients from groups B and C (Reith et al 1988;Herrero Sanchez et al 1992;Durand et al 1994).…”

B-cell factor 1 is required for optimal expression of the DRA promoter in B cells.

“…(i) The human XPB protein (34,35) forms heterodimers with c-Fos (42,43) and binds to the TRE response element (4) found in the X2 region of the DRA and DPB promoters (3,43). (ii) NF-S (30) binds to the same sequence of class II promoters, except that NF-S binds to the DQA and DPA but not the DRA promoters.…”