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Mol. Cell. Biol. doi:10.1128/MCB.00905-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Pu.1 locus is differentially regulated at the level of chromatin structure and non-coding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis

University of Leeds, Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds LS9 7TF, UK, Hematology/Oncology Division, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA

^* To whom correspondence should be addressed. Email: c.bonifer{at}leeds.ac.uk.

	Abstract

The Ets-family transcription factor PU.1 is crucial for the regulation of hematopoietic development. Pu.1 is activated in hematopoietic stem cells and is expressed in mast cells, B cells, granulocytes and macrophages, but is switched off in T cells. Many of the transcription factors regulating Pu.1 have been identified, but little is known about how they organize Pu.1 chromatin in development. To this end we analyzed the Pu.1 promoter and the upstream-regulatory element (URE) using in vivo footprinting and chromatin immunoprecipitation assays. In B cells, Pu.1 was bound by a different set of transcription factors than in myeloid cells and adopted alternative chromatin architectures. In T cells, Pu.1 chromatin at the URE was open and the same transcription factor binding sites were occupied as in B cells. The transcription factor RUNX1 was bound to the URE in precursor cells, but binding was down-regulated in maturing cells. In PU.1 knock-out precursor cells, the Ets factor Fli-1 compensated for the lack of PU.1 and both proteins could occupy a subset of Pu.1 cis-elements in PU.1 expressing cells. In addition, we identified novel tissue-specifically regulated non-coding transcripts originating from the URE. Our results provide important insights into how an overlapping, but different set of transcription factors programs tissue-specific chromatin structures in the hematopoietic system.

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