Id |
Subject |
Object |
Predicate |
Lexical cue |
S1 |
0-125 |
Sentence |
denotes |
PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene. |
S2 |
126-190 |
Sentence |
denotes |
Growth factor receptors play an important role in hematopoiesis. |
S3 |
191-476 |
Sentence |
denotes |
In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis, we initiated a study investigating the transcription factors activating the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha gene. |
S4 |
477-715 |
Sentence |
denotes |
Here, we demonstrate that the human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue-specific fashion in myelomonocytic cells, which correlates with its expression pattern as analyzed by reverse transcription PCR. |
S5 |
716-877 |
Sentence |
denotes |
The GM-CSF receptor alpha promoter contains an important functional site between positions -53 and -41 as identified by deletion analysis of reporter constructs. |
S6 |
878-972 |
Sentence |
denotes |
We show that the myeloid and B cell transcription factor PU.1 binds specifically to this site. |
S7 |
973-1174 |
Sentence |
denotes |
Furthermore, we demonstrate that a CCAAT site located upstream of the PU.1 site between positions -70 and -54 is involved in positive-negative regulation of the GM-CSF receptor alpha promoter activity. |
S8 |
1175-1299 |
Sentence |
denotes |
C/EBP alpha is the major CCAAT/enhancer-binding protein (C/EBP) form binding to this site in nuclear extracts of U937 cells. |
S9 |
1300-1514 |
Sentence |
denotes |
Point mutations of either the PU.1 site or the C/EBP site that abolish the binding of the respective factors result in a significant decrease of GM-CSF receptor alpha promoter activity in myelomonocytic cells only. |
S10 |
1515-1706 |
Sentence |
denotes |
Furthermore, we demonstrate that in myeloid and B cell extracts, PU.1 forms a novel, specific, more slowly migrating complex (PU-SF) when binding the GM-CSF receptor alpha promoter PU.1 site. |
S11 |
1707-1806 |
Sentence |
denotes |
This is the first demonstration of a specific interaction with PU.1 on a myeloid PU.1 binding site. |
S12 |
1807-2085 |
Sentence |
denotes |
The novel complex is distinct from that described previously as binding to B cell enhancer sites and can be formed by addition of PU.1 to extracts from certain nonmyeloid cell types which do not express PU.1, including T cells and epithelial cells, but not from erythroid cells. |
S13 |
2086-2281 |
Sentence |
denotes |
Furthermore, we demonstrate that the PU-SF complex binds to PU.1 sites found on a number of myeloid promoters, and its formation requires an intact PU.1 site adjacent to a single-stranded region. |
S14 |
2282-2369 |
Sentence |
denotes |
Expression of PU.1 in nonmyeloid cells can activate the GM-CSF receptor alpha promoter. |
S15 |
2370-2639 |
Sentence |
denotes |
Deletion of the amino-terminal region of PU.1 results in a failure to form the PU-SF complex and in a concomitant loss of transactivation, suggesting that formation of the PU-SF complex is of functional importance for the activity of the GM-CSF receptor alpha promoter. |
S16 |
2640-2752 |
Sentence |
denotes |
Finally, we demonstrate that C/EBP alpha can also active the GM-CSF receptor alpha promoter in nonmyeloid cells. |
S17 |
2753-3015 |
Sentence |
denotes |
These results suggest that PU.1 and C/EBP alpha direct the cell-type-specific expression of GM-CSF receptor alpha, further establish the role of PU.1 as a key regulator of hematopoiesis, and point to C/EBP alpha as an additional important factor in this process. |