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

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...

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Published in:Molecular and cellular biology Vol. 27; no. 21; p. 7425
Main Authors: Hoogenkamp, Maarten, Krysinska, Hanna, Ingram, Richard, Huang, Gang, Barlow, Rachael, Clarke, Deborah, Ebralidze, Alexander, Zhang, Pu, Tagoh, Hiromi, Cockerill, Peter N, Tenen, Daniel G, Bonifer, Constanze
Format: Journal Article
Language:English
Published: United States 01.11.2007
Subjects:
Animals
B-Lymphocytes - enzymology
B-Lymphocytes - metabolism
Base Sequence
Cell Differentiation
Cells, Cultured
Chromatin - chemistry
Core Binding Factor Alpha 2 Subunit - metabolism
Gene Expression Regulation, Developmental
Hematopoiesis - genetics
Macrophages - enzymology
Macrophages - metabolism
Mice
Molecular Sequence Data
Myeloid Cells - cytology
Myeloid Cells - metabolism
Nucleic Acid Conformation
Promoter Regions, Genetic - genetics
Protein Binding
Proto-Oncogene Proteins - genetics
RNA Polymerase II - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Untranslated - genetics
T-Lymphocytes - enzymology
T-Lymphocytes - metabolism
Trans-Activators - genetics
Transcription Factors - metabolism
Transcription, Genetic
ISSN:0270-7306
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Summary: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.
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ISSN:0270-7306
DOI:10.1128/MCB.00905-07