Intranuclear targeting of AML/CBFα regulatory factors to nuclear matrix-associated transcriptional domains

Congmei Zeng, Sandra Mcneil, Shirwin Pockwinse, Jeffrey Nickerson, Lindsay Shopland, Jeanne B. Lawrence, Sheldon Penman, Scott Hiebert, Jane B. Lian, Andre J van Wijnen, Janet L. Stein, Gary S. Stein

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146 Scopus citations

Abstract

The AML/CBFα runt transcription factors are key regulators of hematopoietic and bone tissue-specific gene expression. These factors contain a 31-amino acid nuclear matrix targeting signal that supports association with the nuclear matrix. We determined that the AML/CBFα factors must bind to the nuclear matrix to exert control of transcription. Fusing the nuclear matrix targeting signal to the GAL4 DNA binding domain transactivates a genomically integrated GALA responsive reporter gene. These data suggest that AML/CBFα must associate with the nuclear matrix to effect transcription. We used fluorescence labeling of epitopetagged AML-1B (CBFA2) to show it colocalizes with a subset of hyperphosphorylated RNA polymerase II molecules concentrated in loci and linked to the nuclear matrix. This association of AML-1B with RNA polymerase II requires active transcription and a functional DNA binding domain. The nuclear matrix domains that contain AML-1B are distinct from SC35 RNA processing domains. Our results suggest two of the requirements for AML-dependent transcription initiation by RNA polymerase II are association of AML-1B with the nuclear matrix together with specific binding of AML to gene promoters.

Original languageEnglish (US)
Pages (from-to)1585-1589
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Zeng, C., Mcneil, S., Pockwinse, S., Nickerson, J., Shopland, L., Lawrence, J. B., Penman, S., Hiebert, S., Lian, J. B., van Wijnen, A. J., Stein, J. L., & Stein, G. S. (1998). Intranuclear targeting of AML/CBFα regulatory factors to nuclear matrix-associated transcriptional domains. Proceedings of the National Academy of Sciences of the United States of America, 95(4), 1585-1589. https://doi.org/10.1073/pnas.95.4.1585