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Department of Pulmonary Diseases, University Hospital Utrecht, Utrecht, The Netherlands
The common ß-chain (ßc) is the main signaling component of the
heterodimeric receptors for IL-3, IL-5, and GM-CSF and is primarily
expressed on myeloid cells. The proximal ßc promoter is regulated by
GGAA binding proteins, including PU.1, a hemopoietic specific member of
the Ets family. However, it is not likely that PU.1 alone accounts for
the myeloid-restricted expression of the ßc subunit. Here we describe
the identification of a C/EBP binding enhancer that is located 2 kb
upstream of the transcription start site. The enhancer contains two
elements that bind C/EBP
and -ß in U937 cells, while C/EBP
is
also bound in extracts of HL-60 cells. Importantly, deletion of the
enhancer or mutation of either of one of the C/EBP sites results in a
complete loss of promoter activity in cell lines as well as in primary
cells, showing the importance of C/EBP members in ßc gene activation.
We further show that PU.1 has to cooperate with C/EBP proteins to
induce ßc transcription. Since the ßc is already expressed on
CD34+ cells, these results demonstrate that both C/EBP and
PU.1 are not only important for the myeloid-specific gene regulation at
later stages of myeloid differentiation.
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