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 to a region in the proteins encoded by a family of interferon-inducible mouse genes, designated Ifi-201, Ifi- 202, Ifi-203, etc, that are not regulated in a cell- or tissue-specific fashion. However, a new member of the Ifi-200 gene family, D3, is induced in mouse mononuclear phagocytes but not in fibroblasts by interferon. The same 200 amino acid region, duplicated in the mouse Ifi- 200 gene family, is also repeated in the recently characterized human IFI 16 gene that is constitutively expressed specifically in lymphoid cells and is induced in myeloid cells by interferon gamma. The 1.8-kb MNDA mRNA, which contains an interferon-stimulated response element in the 5′ untranslated region, was significantly upregulated in human monocytes exposed to interferon alpha. Characterization of the MNDA gene showed that it is a single-copy gene and localized to human chromosome 1q 21–22 within the large linkage group conserved between mouse and human that contains the Ifi-200 gene family. The IFI 16 gene is also located on human chromosome 1q. Our observations are consistent with the proposal that the MNDA is a member of a cluster of related human interferon-regulated genes, similar to the mouse Ifi-200 gene family. In addition, one mouse gene in the Ifi-200 gene family and the human MNDA and IFI 16 genes show expression and/or regulation restricted to cells of the hematopoietic system, suggesting that these genes participate in blood cell-specific responses to interferons.

Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets

“…CD16 + Mo were distinguished from CD16 - Mo by upregulation of the cell cycle related genes cyclin-dependent kinase inhibitor 1C (CDKN1C, p27, or KIP2, which is a negative regulator of cell proliferation [ 66 ] induced by TGF-β [ 67 ]), and metastasis suppressor 1 (MTSS1, a transcript involved in cytoskeleton organization missing in metastasis [ 68 ]). CD16 - Mo preferentially expressed mRNA for genes encoding the CD1d antigen (member of the MHC family that mediates presentation of primarily lipid/glycolipid antigens to T cells), and myeloid cell nuclear differentiation antigen (MNDA, which is expressed in human monocytes and granulocytes and earlier stage cells in the myeloid lineage [ 69 ]) (Figure 5F ). These results provide evidence that CD16 + Mo represent a more advanced stage of differentiation compared to CD16 - Mo.…”

MNDA dimerizes through a complex motif involving an N‐terminal basic region

“…4 . The C‐terminal 200 aa sequence is conserved between MNDA and another related human gene (IF16) as well as a cluster of mouse genes (202, 204, D3) located on chromosome 1q [3, 34, 35]. The MNDA N‐terminal region is enriched with positive charged amino acids [36].…”

“…Leukemic cell lines expressing MNDA also differentiate in response to retinoid treatment whereas MNDA null lines do not. An analysis of >40 cell lines, peripheral blood, bone marrow and cases of leukemia by immunohistochemical staining as well as Northern and Western blotting confirmed the lineage‐ and stage‐specific expression of MNDA [3, 4]. MNDA is up‐regulated specifically by interferon α in nearly all cells that exhibit constitutive expression.…”

“…Regions essential for MNDA dimerization were mapped to an imperfect leucine zipper and a basic region separated by an uninvolved basic amphipathic α ‐helical region in the N‐terminal half of MNDA. MNDA is a member of the gene 200 cluster of interferon‐regulated genes [3]. Each gene contains one or two copies of a highly conserved 200‐amino‐acid region.…”

Inhibition of Growth by p205: A Nuclear Protein and Putative Tumor Suppressor Expressed during Myeloid Cell Differentiation

“…However, between murine and human proteins, the highest homology exists for the p205 and MNDA polypeptides, which have 44% identity to each other. Like p205, MNDA is expressed in a lineage‐specific manner in myeloid cells [9–11]. Treatment of monocytes, HL‐60 cells, U‐937 cells, and THP‐1 cells with interferons results in robust induction of MNDA mRNA [12].…”