Transcription factor regulating MHC expression CDNA and genomic

Details Transcription factor regulating MHC expression CDNA and genomic Transcription factor regulating MHC expression CDNA and genomic

1997-03-31

1999-06-01

Elliott, George C.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Recombinant dna technique included in method of making a...

435367, 435372, 4353723, 435 6, 536 235, 536 2431, C12P 2100, C12N 510, C12N 1512, C07H 2104

Patent

active

059087625

ABSTRACT:
The present invention relates to NF-X1, a novel DNA binding protein which regulates expression of major histocompatibility complex (MHC) class II molecules, and to DNA sequences which encode the protein as well as recombinant expression of the protein. NF-X1 is a newly identified, cysteine-rich polypeptide which interacts sequence-specifically with the conserved X1 box regulatory element found in the proximal promoters of class II MHC genes. A cysteine-rich domain within NF-X1 contains a motif repeated seven times, and this entire region is necessary and sufficient for both sequence specific binding and effector function. The motif is related to but distinct from the previously described metal-binding protein families: LIM domain and RING finger. NFX.1 mRNA is markedly overexpressed late after induction of cells with interferon-gamma, and this overexpression coincides with a reduction in the level of HLA-DRA transcript in these cells. Overexpression of this protein strongly and specifically represses the transcription of the HLA-DRA gene in MHC class II positive cell lines, indicating that the NF-X1 protein is a transcriptional repressor of MHC class II molecules.

REFERENCES:
patent: 4399216 (1983-08-01), Axel et al.
patent: 4446128 (1984-05-01), Baschang et al.
patent: 5166059 (1992-11-01), Pastan et al.
Noelle, et al., "Regulation of the expression of multiple class II genes in murine B cells by B cell stimulatory factor-1 (BSF-1)," J. Immunol., 137:1718-1723 (1986).
Boss, et al., "Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts," Proc. Natl. Acad. Sci. USA, 83:9139-9143 (1986).
Miwa, et al., "Sequence-specific interactions of nuclear factors with conserved sequences of human class II major histocompatibility complex genes," Proc. Natl. Acad. Sci. USA, 84:4939-4943 (1987).
Didier, et al., "Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box," Proc. Natl. Acad. Sci. USA, 85:7322-7326 (1988).
Reith, et al., "Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X," Cell, 53:897-906 (1988).
Latron, et al., "Active suppression of major histocompatibility complex class II gene expression during differentiation from B cells to plasma cells," Proc. Natl. Acad. Sci. USA, 85:2229-2233 (1988).
Ono, et al., "Interferon-.gamma. induces transcription and differential expression of MHC genes in rat insulinoma cell line RINm5F," Diabetes, 38:911-916 (1989).
Reith, et al., "MHC class II regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain," Genes & Dev., 4:1528-1540 (1990).
Liou, et al., "A new member of the leucine zipper class of proteins that binds to the HLA-DR.alpha. promoter," Science, 247:1581-1584 (1990).
Kara, et al., "A cDNA for a human Cyclic AMP Response Element-binding protein which is distinct from CREB and expressed preferentially in brain," Mol. Cell. Biol., 10:1347-1357 (1990).
Andersson, et al., "NF-X2 that binds to the DRA X2-box is activator protein 1. Expression cloning of c-Jun," J. Immunol., 145:3456-3462 (1990).
Benoist, et al., "Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet," Annu. Rev. Immunol., 8:681-715 (1990).
Klemsz, et al., "The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene," Cell, 61:113-124 (1990).
Ono, et al., "Human X-box-binding protein 1 is required for the transcription of a subset of human class II major histocompatibility genes and forms a heterodimer with c-fos," Proc. Natl. Acad. Sci. USA, 88:4309-4312 (1991).
Ono, et al., "An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP," J. Exp. Med., 173:629-637 (1991).
***Cogswell, et al., "Transcriptional regulation of the HLA-DRA gene," Crit. Rev. Immunol., 11:87-112 (1991).
Ono, et al., "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," Proc. Natl. Acad. Sci. USA, 88:4304-4308 (1991).
Viville, et al., "The E.alpha. promoter: a linker-scanning analysis," J. Immunol., 146:3211-3217 (1991).
Kara, et al., "In vivo footprinting of MCH class II genes: Bare promoters in the Bare Lymphocyte Syndrome," Science, 252:709-712 (1991).
Wright, et al., "In vivo footprint analysis of the HLA-DRA gene promoter: Cell-specific interaction at the octamer site and up-regulation of X box binding by interferon .gamma.," Proc. Natl. Acad. Sci. USA, 89:7601-7605 (1992).
Glimcher, et al., "Sequences and factors: a guide to MHC class-II transcription," Annu. Rev. Immunol., 10:13-49 (1992).
Li, et al., "Intro-exon organization of the NF-Y genes. Tissue-specific splicing modifies an activation domain," J. Biol. Chem., 267:8984-8990 (1992).
Zeleznik-Le, et al., "The B cell-specific nuclear factor OTF-2 positively regulates transcription of the human class II transplantation gene, DRA," J. Biol. Chem., 267:7677-7682 (1992).
Steimle, et al., "Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or Bare Lymphocyte Syndrome)," Cell 75:135-146 (1993).
Steimle, et al., "Regulation of MHC class II expression by interferon-.gamma. mediated by the transactivator gene CIITA," Science, 265:106-109 (1994).
Brand, et al., "Characterization of a "silencer" in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer," Cell, 41:41-48 (1985).
Goodbourn, et al., "The human .beta.-interferon gene enhancer is under negative control," Cell, 45:601-610 (1986).
***Ma, et al., "The carboxy-terminal 30 amino acids of GAL4 are recognized by GAL80," Cell, 50:137-142 (1987).
Gaul, et al., "Analysis of Kruppel protein distribution during early Drosophila development reveals posttranscriptional regulation," Cell, 50:639-647 (1987).
Keller, et al., "Identification of an inducible factor that binds to a positive regulatory element of the human .beta.-interferon gene," Proc. Natl. Acad. Sci. USA, 85:3309-3313 (1988).
Baeuerle, et al., "I.kappa.B: A specific inhibitor of the NF.kappa.B transcription factor," Science, 242:540-546 (1988).
Levine, et al., "Transcriptional repression of eukaryotic promoters," Cell, 59:405-408 (1989).
Drouin, et al., "Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription," Mol. Cell. Biol., 9:5305-5314 (1989).
Freyd, et al., "Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11", Nature, 344:876-879 (1990).
Licht, et al., "Drosophila Kruppel protein is a transcriptional repressor," Nature, 346:76-79 (1990).
Driggers, et al., "An interferon .gamma.-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes," Proc. Natl. Acad. Sci. USA, 87:3743-3747 (1990).
***Whittemore, et al., "Postinduction repression of the .beta.-interferon gene is mediated through two positive regulatory domains," Proc. Natl. Acad. Sci. USA, 87:7799-7803 (1990).
Freemont, et al., "A novel cysteine-rich sequence motif," Cell, 64:483-484 (1991).
Keller, et al., "Identification and characterization of a novel repressor of .beta.-interferon gene expression," Gene & Dev., 5:868-879 (1991).
Keller, et al., "Only two of the five zinc fingers of the eukaryotic transcriptional repressor PRDI-BF1 are required for sequence-specific DNA binding," Mol. Cell. Biol., 12:1940-1949 (1992).
Desjarlais, et al., "Use of zinc-finger consensus sequence framework and specificity rules to design specific DNA binding proteins," Proc. Natl. Acad. Sci. USA, 90:2256-2260 (1993).
Song, "A Novel Cysteine-Rich Sequence-Specific DNA-Binding Protein Interacts with the Conserved X-Box Motif of the Human MHC Class II Genes and Functions as a Transcriptional Repressor," FASEB J.,

Affiliated with

Also associated with

Rating

Transcription factor regulating MHC expression CDNA and genomic does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Transcription factor regulating MHC expression CDNA and genomic , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transcription factor regulating MHC expression CDNA and genomic will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-954560