The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family: Interactions with the osteocalcin gene promoter

Harold L. Merriman, Andre J van Wijnen, Scott Hiebert, Joseph P. Bidwell, Edward Fey, Jane Lian, Janet Stein, Gary S. Stein

Research output: Contribution to journalArticle

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Abstract

The nuclear matrix protein, NMP-2, was originally identified as an osteoblast-specific DNA-binding complex localized exclusively to the nuclear matrix. NMP-2 was shown to recognize two binding sites, site A (nt -605 to -599) and site B (nt -441 to -435), in the rat bone-specific osteocalcin gene promoter. This study shows that the NMP-2 binding sites A and B as well as a third NMP-2 binding site (nt -135 to -130) constitute a consensus sequence, A TGC TGGT, and represent an AML-1 recognition motif. AML-1 is a member of the AML transcription factor family which is associated with acute myelogenous leukemia and binds to the sequence TGC TGGT via its DNA-binding runt domain. Electrophoretic mobility shift assays reveal that a component of NMP-2 is a member of the AML/PEBP2/ runt domain transcription factor family based on cross-competition with AML-1 consensus oligonucleotide. Limited immunoreactivity of NMP-2 with a polyclonal N-terminal AML-1 antibody and inability of the AML-1 partner protein CBF-β to form complexes with NMP-2 indicate that NMP-2 is not identical to AML-1 but represents a variant AML/PEBP2/runt domain protein. Western and Northern blots reveal the presence of multiple AML-related proteins and AML-1 transcripts in several osseous cell lines. Furthermore, our results indicate that AML family members may selectively partition between nuclear matrix and nonmatrix compartments. Because proteins that contain a runt domain are implicated in tissue-specific transcriptional regulation, our results support the concept that the nuclear matrix mediates osteoblast-specific expression of the osteocalcin gene.

Original languageEnglish (US)
Pages (from-to)13125-13132
Number of pages8
JournalBiochemistry
Volume34
Issue number40
StatePublished - 1995
Externally publishedYes

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Core Binding Factor alpha Subunits
Nuclear Matrix-Associated Proteins
Osteocalcin
Transcription Factors
Genes
Tissue
Nuclear Matrix
Binding Sites
Osteoblasts
Proteins
Electrophoretic mobility
nuclear matrix protein 2
DNA
Consensus Sequence
Oligonucleotides
Electrophoretic Mobility Shift Assay
Rats
Acute Myeloid Leukemia
Assays
Northern Blotting

ASJC Scopus subject areas

  • Biochemistry

Cite this

Merriman, H. L., van Wijnen, A. J., Hiebert, S., Bidwell, J. P., Fey, E., Lian, J., ... Stein, G. S. (1995). The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family: Interactions with the osteocalcin gene promoter. Biochemistry, 34(40), 13125-13132.

The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family : Interactions with the osteocalcin gene promoter. / Merriman, Harold L.; van Wijnen, Andre J; Hiebert, Scott; Bidwell, Joseph P.; Fey, Edward; Lian, Jane; Stein, Janet; Stein, Gary S.

In: Biochemistry, Vol. 34, No. 40, 1995, p. 13125-13132.

Research output: Contribution to journalArticle

Merriman, HL, van Wijnen, AJ, Hiebert, S, Bidwell, JP, Fey, E, Lian, J, Stein, J & Stein, GS 1995, 'The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family: Interactions with the osteocalcin gene promoter', Biochemistry, vol. 34, no. 40, pp. 13125-13132.
Merriman, Harold L. ; van Wijnen, Andre J ; Hiebert, Scott ; Bidwell, Joseph P. ; Fey, Edward ; Lian, Jane ; Stein, Janet ; Stein, Gary S. / The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family : Interactions with the osteocalcin gene promoter. In: Biochemistry. 1995 ; Vol. 34, No. 40. pp. 13125-13132.
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AU - Lian, Jane

AU - Stein, Janet

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