1: Blood. 2004 Oct 1;104(7):2027-34. Epub 2004 Jun 8. 

Upstream stimulatory factors stimulate transcription through E-box motifs in the
PF4 gene in megakaryocytes.

Okada Y, Matsuura E, Tozuka Z, Nagai R, Watanabe A, Matsumoto K, Yasui K,
Jackman RW, Nakano T, Doi T.

Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka,
Japan.

Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We
previously demonstrated that the homeodomain proteins (myeloid ecotropic
integration site 1 [MEIS1], Pbx-regulating protein 1 [PREP1], and pre-B-cell
leukemia transcription factors [PBXs]) bind to the novel regulatory element
tandem repeat of MEIS1 binding element [TME] and transactivate the rat PF4
promoter. In the present study, we investigated and identified other TME binding
proteins in megakaryocytic HEL cells using mass spectrometry. Among identified
proteins, we focused on upstream stimulatory factor (USF1) and USF2 and
investigated their effects on the PF4 promoter. USF1 and 2 bound to the E-box
motif in the TME and strongly transactivated the PF4 promoter. Furthermore,
physiologic bindings of USF1 and 2 to the TME in rat megakaryocytes were
demonstrated by the chromatin immunoprecipitation (ChIP) assay. Interestingly,
the E-box motif in the TME was conserved in TME-like sequences of both the human
and mouse PF4 promoters. USF1 and 2 also bound to the human TME-like sequence
and transactivated the human PF4 promoter. Expressions of USF1 and 2 were
detected by reverse-transcriptase-polymerase chain reaction (RT-PCR) in the
human megakaryocytes derived from CD34+ cells. Thus, these studies demonstrate
that the novel TME binding transcription factors, USF1 and 2, transactivate rat
and human PF4 promoters and may play an important role in megakaryocytic gene
expression.

PMID: 15187018 [PubMed - indexed for MEDLINE]


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