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 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.11.2007
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| ISSN: | 0270-7306 |
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| 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. 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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| AbstractList | 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. 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.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. |
| Author | Ingram, Richard Clarke, Deborah Hoogenkamp, Maarten Bonifer, Constanze Ebralidze, Alexander Cockerill, Peter N Huang, Gang Barlow, Rachael Tagoh, Hiromi Tenen, Daniel G Krysinska, Hanna Zhang, Pu |
| Author_xml | – sequence: 1 givenname: Maarten surname: Hoogenkamp fullname: Hoogenkamp, Maarten organization: University of Leeds, Leeds Institute of Molecular Medicine, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, United Kingdom – sequence: 2 givenname: Hanna surname: Krysinska fullname: Krysinska, Hanna – sequence: 3 givenname: Richard surname: Ingram fullname: Ingram, Richard – sequence: 4 givenname: Gang surname: Huang fullname: Huang, Gang – sequence: 5 givenname: Rachael surname: Barlow fullname: Barlow, Rachael – sequence: 6 givenname: Deborah surname: Clarke fullname: Clarke, Deborah – sequence: 7 givenname: Alexander surname: Ebralidze fullname: Ebralidze, Alexander – sequence: 8 givenname: Pu surname: Zhang fullname: Zhang, Pu – sequence: 9 givenname: Hiromi surname: Tagoh fullname: Tagoh, Hiromi – sequence: 10 givenname: Peter N surname: Cockerill fullname: Cockerill, Peter N – sequence: 11 givenname: Daniel G surname: Tenen fullname: Tenen, Daniel G – sequence: 12 givenname: Constanze surname: Bonifer fullname: Bonifer, Constanze |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17785440$$D View this record in MEDLINE/PubMed |
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| Snippet | 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... |
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| SubjectTerms | 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 |
| Title | 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 |
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