Journal
ONCOGENE
Volume 27, Issue 19, Pages 2772-2779Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1210940
Keywords
C/EBP alpha; C-jun; PU.1; myeloid
Funding
- NHLBI NIH HHS [R01 HL082948-03, R01 HL082948-02, R01 HL082948, R01 HL082948-01] Funding Source: Medline
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The basic-region leucine zipper (BR-LZ or bZIP) transcription factors dimerize via their LZ domains to position the adjacent BRs for DNA binding. Members of the C/EBP, AP-1 and CREB/ATF bZIP subfamilies form homodimeric or heterodimeric complexes with other members of the same subset and bind-specific DNA motifs. Here we demonstrate that C/EBP alpha also zippers with AP-1 proteins and that this interaction allows contact with novel DNA elements and induction of monocyte lineage commitment in myeloid progenitors. A leucine zipper swap: gel shift assay demonstrates that C/EBP alpha zippers with c-Jun, JunB or c-Fos, but not with c-Maf or MafB. To evaluate activities of specific homodimers or heterodimers we utilized LZs with acid (LZE) or basic (LZK) residues in their salt bridge positions. C/EBP alpha LZE: C/EBP alpha LZK preferentially binds a C/EBP site, c-JunLZE: c-FosLZK an AP-1 site and C/EBP alpha LZE: c-JunLZK a hybrid element identified as TTGCGTCAT by oligonucleotide selection. In murine myeloid progenitors, C/EBP alpha:c-Jun or C/EBP alpha:c-Fos LZE: LZK heterodimers induce monocyte lineage commitment with markedly increased potency compared with C/EBP alpha or c-Jun homodimers or c-Jun: c-Fos heterodimers, demonstrating a positive functional consequence of C/EBP: AP-1 bZIP subfamily interaction. C/EBP alpha:cJun binds and activates the endogenous PU.1 promoter, providing one mechanism for induction of monopoiesis by this complex.
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