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

被引:149
作者
Zeng, CM
McNeil, S
Pockwinse, S
Nickerson, J
Shopland, L
Lawrence, JB
Penman, S
Hiebert, S
Lian, JB
van Wijnen, AJ
Stein, JL
Stein, GS
机构
[1] Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA
[2] Univ Massachusetts, Med Ctr, Ctr Canc, Worcester, MA 01655 USA
[3] MIT, Dept Biol, Cambridge, MA 02139 USA
[4] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA
关键词
D O I
10.1073/pnas.95.4.1585
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The AML/CBF alpha 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/CBF alpha 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 GAL4 responsive reporter gene. These data suggest that AML/CBF alpha must associate with the nuclear matrix to effect transcription, We used fluorescence labeling of epitope-tagged AML-1B (CBFA2) to show it colocalizes with a subset of hyperphosphorylated RNA polymerase II molecules concentrated in foci 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.
引用
收藏
页码:1585 / 1589
页数:5
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