Subcellular partitioning of transcription factors during osteoblast differentiation: developmental association of the AML/CBF alpha/PEBP2 alpha-related transcription factor-NMP-2 with the nuclear matrix.
The subnuclear location of transcription factors may functionally contribute to the regulation of gene expression. Several classes of gene regulators associate with the nuclear matrix in a cell type, cell growth, or cell cycle related-manner. To understand control of nuclear matrix-transcription factor interactions during tissue development, we systematically analyzed the subnuclear partitioning of a panel of transcription factors (including NMP-1/YY-1, NMP-2/AML, AP-1, and SP-1) during osteoblast differentiation using biochemical fractionation and gel shift analyses. We show that nuclear matrix association of the tissue-specific AML transcription factor NMP-2, but not the ubiquitous transcription factor YY1, is developmentally upregulated during osteoblast differentiation. Moreover, we show that there are multiple AML isoforms in mature osteoblasts, consistent with the multiplicity of AML factors that are derived from different genes and alternatively spliced cDNAs. These AML isoforms include proteins derived from the AML-3 gene and partition between distinct subcellular compartments. We conclude that the selective partitioning of the YY1 and AML transcription factors with the nuclear matrix involves a discriminatory mechanism that targets different classes and specific isoforms of gene regulatory factors to the nuclear matrix at distinct developmental stages. Our results are consistent with a role for the nuclear matrix in regulating the expression of bone-tissue specific genes during development of the mature osteocytic phenotype.
Lindenmuth
D M
DM
Department of Cell Biology, University of Massachusetts Medical School and Cancer Center, Worcester, 01655, USA.
van Wijnen
A J
AJ
Hiebert
S
S
Stein
J L
JL
Lian
J B
JB
Stein
G S
GS
D000818:Animals; D034961:Antigens, Nuclear; D002451:Cell Compartmentation; D050676:Core Binding Factor Alpha 2 Subunit; D050660:Core Binding Factors; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D018507:Gene Expression Regulation, Developmental; D009363:Neoplasm Proteins; D015530:Nuclear Matrix / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051381:Rats; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D050986:YY1 Transcription Factor
D034961:Antigens, Nuclear; D050676:Core Binding Factor Alpha 2 Subunit; D050660:Core Binding Factors; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C493727:Runx1 protein, rat; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494700:Yy1 protein, rat; C087950:nuclear matrix protein 2