Two promoters control the mouse Nmp4/CIZ transcription factor gene.
Nmp4/CIZ proteins (nuclear matrix protein 4/cas interacting zinc finger protein) contribute to gene regulation in bone, blood, and testis. In osteoblasts, they govern the magnitude of gene response to osteotropic factors like parathyroid hormone (PTH). Nmp4/CIZ is recurrently involved in acute leukemia and it has been implicated in spermatogenesis. However, these conserved proteins, derived from a single gene, are expressed in numerous tissues indicative of a more generalized housekeeping function in addition to their tissue-specific roles. To address how Nmp4/CIZ expression is governed, we characterized the 5' regulatory region of the mouse Nmp4 gene, located on chromosome 6. Two adjacent promoters P(1) [-2521 nucleotide (nt)/-597 nt] and P(2) (-2521 nt/+1 nt) initiate transcription of alternative first exons (U(1) and U(2)). Both promoters lack TATA and CCAAT boxes but contain initiator sites and CpG islands. Northern analysis revealed expression of both U(1) and U(2) in numerous adult tissues consistent with the constitutive and ubiquitous activity of a housekeeping gene. Sequence analysis identified numerous potential transcription factor-binding sites significant to osteogenesis, hematopoeisis, and gonadal development. The promoters are active in both osteoblast-like cells and in the M12 B-lymphocyte cell line. Low doses of PTH attenuated P(1)/P(2) activity in osteoblast-like cells. The Nmp4/CIZ promoters are autoregulated and deletion analysis identified regions that drive P(1) and P(2) basal activities as well as regions that contain positive and negative regulatory elements affecting transcription. The Nmp4/CIZ promoters comprise a genomic regulatory architecture that supports constitutive expression as well as cell- and tissue-specific regulation.
Alvarez
Marta
M
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Medical Science Bldg 5035, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Shah
Rita
R
Rhodes
Simon J
SJ
Bidwell
Joseph P
JP
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018899:CpG Islands; D005091:Exons / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005809:Genes, Regulator / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D034521:Nuclear Matrix-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity; D010012:Osteogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics* / Q000502:physiology
D034521:Nuclear Matrix-Associated Proteins; D014157:Transcription Factors; C499081:Zfp384 protein, mouse; C440548:Zfp384 protein, rat