Granulocyte inducer C/EBP inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions
نویسندگان
چکیده
Several transcription factors have been implicated as playing a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of myeloid and lymphoid lineages, whereas the transcription factor CCAAT–enhancer binding protein family member C/EBP is essential for granulocyte development. We present here the first evidence that C/EBP blocks the function of PU.1. PU.1 and C/EBP interact physically and colocalize in myeloid cells. As a consequence of this interaction, C/EBP can inhibit the function of PU.1 to activate a minimal promoter containing only PU.1 DNAbinding sites. We further demonstrate that the leucine zipper in the DNA-binding domain of C/EBP interacts with the 3/ 4 region in the DNA-binding domain of PU.1 and as a result displaces the PU.1 coactivator c-Jun. Finally, C/EBP blocks PU.1induced dendritic cell development from CD34 human cord blood cells. The functional blocking of PU.1 by C/EBP could be the mechanism by which C/EBP inhibits cell fates specified by PU.1 and directs cell development to the granulocyte lineage. (Blood. 2002;100:483-490)
منابع مشابه
Granulocyte inducer C/EBPalpha inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions.
Several transcription factors have been implicated as playing a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of myeloid and lymphoid lineages, whereas the transcription factor CCAAT-enhancer binding protein family member C/EBPalpha is essential for granulocyte development. We present here the first evidence that C/EBPalpha blocks the function o...
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