This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00905-07v1 27/21/7425    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hoogenkamp, M. Articles by Bonifer, C. Search for Related Content PubMed PubMed Citation Articles by Hoogenkamp, M. Articles by Bonifer, C.

The Pu.1 Locus Is Differentially Regulated at the Level of Chromatin Structure and Noncoding Transcription by Alternate Mechanisms at Distinct Developmental Stages of Hematopoiesis

Maarten Hoogenkamp,¹ Hanna Krysinska,¹ Richard Ingram,¹ Gang Huang,^2, Rachael Barlow,¹ Deborah Clarke,¹ Alexander Ebralidze,² Pu Zhang,² Hiromi Tagoh,¹ Peter N. Cockerill,¹ Daniel G. Tenen,² and Constanze Bonifer^1*

Section of Experimental Haematology, Leeds Institute of Molecular Medicine, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, United Kingdom,¹ Hematology/Oncology Division, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts 02115²

Received 22 May 2007/ Returned for modification 11 June 2007/ Accepted 10 August 2007

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. 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 set of transcription factors different from that 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 knockout 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 URE-derived noncoding transcripts subject to tissue-specific regulation. Our results provide important insights into how overlapping, but different, sets of transcription factors program tissue-specific chromatin structures in the hematopoietic system.

Published ahead of print on 4 September 2007.

Present address: Laboratory of Molecular Aspects of Hematopoiesis, Memorial Sloan-Kettering Cancer Center, Zuckerman Research Center, 408 East 69th St., New York, NY 10021.

This article has been cited by other articles:

• Ingram, R., Gao, C., LeBon, J., Liu, Q., Mayoral, R. J., Sommer, S. S., Hoogenkamp, M., Riggs, A. D., Bonifer, C. (2008). PAP-LMPCR for improved, allele-specific footprinting and automated chromatin fine structure analysis. Nucleic Acids Res 36: e19-e19 [Abstract] [Full Text]  
• Zhang, L., Fried, F. B., Guo, H., Friedman, A. D. (2008). Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation. Blood 111: 1193-1200 [Abstract] [Full Text]