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Publication : A compendium of genome-wide hematopoietic transcription factor maps supports the identification of gene regulatory control mechanisms.

First Author  Hannah R Year  2011
Journal  Exp Hematol Volume  39
Issue  5 Pages  531-41
PubMed ID  21338655 Mgi Jnum  J:177964
Mgi Id  MGI:5296741 Doi  10.1016/j.exphem.2011.02.009
Citation  Hannah R, et al. (2011) A compendium of genome-wide hematopoietic transcription factor maps supports the identification of gene regulatory control mechanisms. Exp Hematol 39(5):531-41
abstractText  OBJECTIVE: Key regulators of blood stem cell differentiation into the various mature hematopoietic lineages are commonly encoded by transcription factor genes. Elucidation of transcriptional regulatory mechanisms therefore holds great promise in advancing our understanding of both normal and malignant hematopoiesis. Recent technological advances have enabled the generation of genome-wide transcription factor binding maps using chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). However, transcription factors operate in a combinatorial fashion suggesting that integrated analysis of genome-wide maps for multiple transcription factors will be essential to fully exploit these new genome-scale data sets. MATERIALS AND METHODS: Here we have generated a compendium that integrates 53 ChIP-Seq studies covering 30 factors across all major hematopoietic lineages with a total of 754,380 binding peaks. We also used transgenic mouse assays to validate a newly predicted transcriptional enhancer. RESULTS: Integrated analysis of all 53 ChIP-Seq studies demonstrated that cell-type identity exerts a larger influence on global transcription factor binding patterns than the nature of the individual transcription factors. Furthermore, regions highlighted by multifactor binding within specific gene loci overlap with known regulatory elements and also provide a useful guide for identifying novel elements, as demonstrated by transgenic analysis of a previously unrecognized enhancer in the Maml3 gene locus. CONCLUSIONS: The ChIP-Seq compendium described here provides a valuable resource for the wider research community by accelerating the discovery of transcriptional mechanisms operating in the hematopoietic system.
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