Involvement of the nuclear matrix in the control of skeletal genes: the NMP1 (YY1), NMP2 (Cbfa1), and NMP4 (Nmp4/CIZ) transcription factors.
The functional role of the osteoblast nuclear matrix has been a matter of supposition. Its presumed function as an architectural agent of transcription derives primarily from the low solubility of nuclear matrix proteins and their typical localization into discrete subnuclear domains. In addressing how the nuclear matrix regulates skeletal genes, the authors compare Nmp4, Cbfal, and YY1 for the purpose of profiling osteoblast nuclear matrix transcription factors. All three proteins contribute to the transcription of ECM genes and partition into the osteoblast nuclear matrix via a nuclear matrix targeting domain. The authors propose that osteoblast nuclear matrix transcription factors involved in ECM regulation generally have the capacity to alter DNA geometry and reciprocally respond to DNA as an allosteric ligand. This may allow these proteins to adapt to the local nuclear architecture and generate the pattern of regulation specified by that architecture via unmasking of the appropriate transactivation domains. Osteoblast nuclear matrix transcription factors may also act as transcriptional adaptor molecules by supporting the formation of higher order protein complexes along target gene promoters. The genes encoding all three proteins considered here have trinucleotide repeat domains, although the significance of this is unclear. There is no canonical nuclear matrix binding motif, but finger-like structures may be suited for anchoring proteins to discrete subnuclear domains. Finally, the ability to leave the osteoblast nuclear matrix may be as important to the function of some nuclear matrix transcription factors as their association with this subcompartment.
Bidwell
J P
JP
Department of Anatomy and Cell Biology, Indiana University School of Dentistry, Indianapolis 46202, USA. jbidwell@iupui.edu
Torrungruang
K
K
Alvarez
M
M
Rhodes
S J
SJ
Shah
R
R
Jones
D R
DR
Charoonpatrapong
K
K
Hock
J M
JM
Watt
A J
AJ
D000818:Animals; D034961:Antigens, Nuclear; D001483:Base Sequence; D001842:Bone and Bones / Q000502:physiology*; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015530:Nuclear Matrix / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D050986:YY1 Transcription Factor
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D034521:Nuclear Matrix-Associated Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse; C494700:Yy1 protein, rat; C498621:ZNF384 protein, human; C499081:Zfp384 protein, mouse; C440548:Zfp384 protein, rat; C087950:nuclear matrix protein 2