The human myeloid cell nuclear differentiation antigen gene is one of at least two related interferon-inducible genes located on chromosome 1q that are expressed specifically in hematopoietic cells

Abstract

We have previously shown that the human myeloid cell nuclear differentiation antigen (MNDA) is expressed at both the antigen and mRNA levels specifically in human monocytes and granulocytes and earlier stage cells in the myeloid lineage. A 200 amino acid region of the MNDA is strikingly similar t o a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Mi-201, Mi-202, K-203, etc, that are not regulated in a cell-or tissue-specific fashion. However, a new member of the lfi-ZOO gene family, 03, is induced in mouse mononuclear phagocytes but not in fibroblasts by interferon. The same 200 amino acid region, duplicated in the mouse Mi-ZOO gene family, is also repeated in the recently characterized human IF1 16 gene that is constitutively expressed specifically in lymphoid cells and is induced in myeloid cells by interferon y. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response HE HUMAN MYELOID cell nuclear differentiation antigen (MNDA) is detected only in nuclei of cells of the granulocyte-monocyte lineage.' We also evaluated MNDA expression in 21 cases of human acute leukemia classified by French-American-British (FAB) Group criteria.2 Cases in the FAB M2, M3, M4, and M5 categories, in which myeloid cell maturation is evident, were all positive with variability in percentage of positive cells and in the intensity of the staining reactions. In five cases of acute myeloblastic leukemia without maturation (FAB MI), three were negative and two were positive. The four cases of acute lymphocytic leukemia were all negative. Two cases of biphenotypic acute leukemia and one case of lymphoid blast crisis of chronic granulocytic leukemia were also negative.2 These results indicated that MNDA expression is correlated with granulocyte and monocyte differentiation in cases of acute leukemia. Our MNDA amino acid and cDNA sequence a n a l y~i s~.~ provided insight into its functional significance. The strict nuclear localization of the MNDA in interphase cells is consistent with its containing sequence motifs commonly found in gene regulatory protein^.^ In addition, DNA binding activity of the MNDA was previously demonstrated using DNAprotein cross-linking.5 MNDA contains extended regions of sequence at both the DNA and protein levels similar to a class of mouse genes cluster) that are interferon-ind~cible.~.~ The mouse @-202 and @-204 genes each encode contiguous 200 amino acid (aa) regions that are highly conserved within each protein and between proteins in the family. The recently characterized mouse D3 gene, a new member of the @-ZOO gene family, contains only a single copy of the 200-aa conserved sequence and exhibits a sequence similar to the I$-204 gene outside of the 200-aa conserved sequence that is unique from other members of the @-200 gene family.' The MNDA also contains only a single copy of the 200-aa conserved sequence and more than half of the 67 residues of its NH2 terminal sequence are identical to the NH2 terminal domain of the mouse 204 protein.' In the ...

Molecular Cloning and Expression of an Interferon‐Inducible Protein Encoded by Gene 203 from the Gene 200 Cluster

“…We have presented the complete nucleotide sequence, as well as the corresponding amino acid sequence, of a novel murine cDNA clone of a member of the Ifi 200 gene cluster designated 203. This cDNA encodes a protein with a unique organization, but bearing structural similarities to proteins expressed from the Ifi 200 gene cluster as well as from a cluster of related genes occurring in the human genome on chromosome 1, a region syntenic between mouse and man [6,24,251. The murine Ifi 202 and Ifi 204 genes and the human IF1 16 gene encode two contiguous 200-amino-acid segments, designated a and b, respectively, that are highly conserved among various proteins of the family [6,7,11,251.…”

Evaluation of flow cytometric assessment of myeloid nuclear differentiation antigen expression as a diagnostic marker for myelodysplastic syndromes in a series of 269 patients

“…Myeloid nuclear differentiation antigen (MNDA) is a 407 amino acid nuclear hematopoietic protein of the interferon inducible p200-familiy proteins, and its encoding gene is located at chromosomal band 1q21-22 (23,24). It is capable of DNA binding and mediating protein-protein interaction, thereby slowing down proliferation, modulating cell survival and promoting differentiation (25).…”

Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter: Evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression

“…Genomic DNA was isolated by anion exchange chromatography (Genomic DNA Purification Kit, Qiagen) resulting in an average of 60 µg DNA/10 7 nuclei. Preparation of control non-digested genomic DNA, conditions for restriction enzyme digestion, sample preparation, and Southern blot analysis were essentially as described previously [Briggs et al, 1994a]. Two non-overlapping DNA fragments, as illustrated in Figure 2, were used to prepare 32 P-labeled probes by random hexamer priming.…”

“…MNDA appears to function through interactions with a number of other nuclear proteins [Xie et al, 1995]. MNDA is encoded by a single-copy gene located on chromosome 1q21-22 belonging to a family of interferon-regulated genes [Briggs et al, 1994a]. To delineate the mechanisms responsible for the tight regulation of this gene, an extensive study of the 58 flanking sequence isolated from a genomic clone [Briggs et al, 1994a] was initiated.…”

“…MNDA is encoded by a single-copy gene located on chromosome 1q21-22 belonging to a family of interferon-regulated genes [Briggs et al, 1994a]. To delineate the mechanisms responsible for the tight regulation of this gene, an extensive study of the 58 flanking sequence isolated from a genomic clone [Briggs et al, 1994a] was initiated. This sequence contains functional promoter activity and several regulatory elements consistent with myelomonocytic lineage-specific gene transcription [Kao et al, 1996].…”