Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells

The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established....

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Vydáno v:Blood Ročník 117; číslo 10; s. 2827
Hlavní autoři: Leddin, Mathias, Perrod, Chiara, Hoogenkamp, Maarten, Ghani, Saeed, Assi, Salam, Heinz, Sven, Wilson, Nicola K, Follows, George, Schönheit, Jörg, Vockentanz, Lena, Mosammam, Ali M, Chen, Wei, Tenen, Daniel G, Westhead, David R, Göttgens, Berthold, Bonifer, Constanze, Rosenbauer, Frank
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 10.03.2011
Témata:
Animals
B-Lymphocytes - metabolism
Blotting, Southern
Blotting, Western
Cell Separation
Feedback, Physiological - physiology
Flow Cytometry
Gene Expression
Gene Expression Regulation - genetics
Hematopoiesis - genetics
Humans
Mice
Mice, Transgenic
Myeloid Cells - metabolism
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Regulatory Elements, Transcriptional - genetics
Reverse Transcriptase Polymerase Chain Reaction
Trans-Activators - genetics
Trans-Activators - metabolism
ISSN:1528-0020, 1528-0020
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Popis
Shrnutí:The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type-specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2010-08-302976