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, André J. Van Wijnen, Janet L. Stein, Gary S. Stein

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147 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

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    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