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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bresnick, Emery H. Kim, Shin-il Johnson, Kirby D. |
| Description | Author Affiliation: Johnson KD ( Molecular and Cellular Pharmacology Program, Department of Pharmacology, University of Wisconsin School of Medicine, 383 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA.); |
| Abstract | Changes in transcription factor levels and activities dictate developmental fate. Such a change might affect the full ensemble of target genes for a factor or only uniquely sensitive targets. We investigated the relationship among activity of the hematopoietic transcription factor GATA-1, chromatin occupancy, and target gene sensitivity. Graded activation of GATA-1 in GATA-1-null cells revealed high-, intermediate-, and low-sensitivity targets. GATA-1 activity requirements for occupancy and transcription often correlated. A GATA-1 amino-terminal deletion mutant severely deregulated the low-sensitivity gene Tac-2. Thus, cells expressing different levels of a cell type-specific activator can have qualitatively distinct target gene expression patterns, and factor mutations preferentially deregulate low-sensitivity genes. Unlike other target genes, GATA-1-mediated Tac-2 regulation was bimodal, with activation followed by repression, and the coregulator Friend of GATA-1 (FOG-1) selectively mediated repression. A GATA-1 mutant defective in FOG-1 binding occupied a Tac-2 regulatory region at levels higher than wild-type GATA-1, whereas FOG-1 facilitated chromatin occupancy at a distinct target site. These results indicate that FOG-1 is a determinant of GATA factor target gene sensitivity by either facilitating or opposing chromatin occupancy. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | GATA1 Transcription Factor Metabolism Gene Expression Profiling Gene Expression Regulation Genetics Cell Line Gene Deletion Neurokinin B Organ Specificity Protein Binding Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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