1: J Cell Biochem. 1997 Jul 1;66(1):123-32. 

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.

Lindenmuth DM, van Wijnen AJ, Hiebert S, Stein JL, Lian JB, Stein GS.

Department of Cell Biology, University of Massachusetts Medical School and
Cancer Center, Worcester, 01655, USA.

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.

PMID: 9215534 [PubMed - indexed for MEDLINE]


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