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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1056-1067. Prepublished online as a Blood First Edition Paper on June 12, 2008; DOI 10.1182/blood-2007-12-128900. This Article Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2007-12-128900v1 112/4/1056    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kassouf, M. T Articles by Porcher, C. Search for Related Content PubMed PubMed Citation Articles by Kassouf, M. T Articles by Porcher, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 17, 2007 Accepted April 24, 2008 Differential use of SCL/TAL-1 DNA-binding domain in developmental hematopoiesis Mira T Kassouf, Hedia Chagraoui, Paresh Vyas, and Catherine Porcher* MRC Molecular Haematology Unit, Weatherall Insitute of Molecular Medicine, University of Oxford, Oxford, United Kingdom * Corresponding author; email: catherine.porcher{at}imm.ox.ac.uk. Dissecting the molecular mechanisms utilised by developmental regulators is essential to understand tissue specification/differentiation. SCL/TAL-1 is a basic-Helix-Loop-Helix transcription factor absolutely critical for hematopoietic stem/progenitor cell specification and lineage maturation. Using in vitro and forced expression experimental systems, we previously suggested that SCL might have DNA-binding independent functions. Here, to assess the requirements for SCL DNA-binding activity in vivo, we examined hematopoietic development in mice carrying a germline DNA-binding mutation. Remarkably, in contrast to complete absence of hematopoiesis and early lethality in scl-null embryos, specification of hematopoietic cells occurred in homozygous mutant embryos, indicating that direct DNA-binding is dispensable for this process. Lethality was forestalled to later in development, although some mice survived to adulthood. Anemia was documented throughout development and in adulthood. Cellular and molecular studies demonstrated critical requirements for SCL direct DNA-binding in red cell maturation and indicated that scl expression is positively autoregulated in terminally differentiating erythroid cells. Thus, different mechanisms of SCL's action predominate depending on the developmental/cellular context: indirect DNA-binding activities and/or sequestration of other nuclear regulators are sufficient in specification processes whereas direct DNA-binding functions with transcriptional autoregulation are critically required in terminal maturation processes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Tripic, W. Deng, Y. Cheng, Y. Zhang, C. R. Vakoc, G. D. Gregory, R. C. Hardison, and G. A. Blobel SCL and associated proteins distinguish active from repressive GATA transcription factor complexes Blood, March 5, 2009; 113(10): 2191 - 2201. [Abstract] [Full Text] [PDF]

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