Genome-wide identification of TAL1's functional targets: Insights into its mechanisms of action in primary erythroid cells
- Mira T. Kassouf1,
- Jim R. Hughes1,
- Stephen Taylor2,
- Simon J. McGowan2,
- Shamit Soneji1,
- Angela L. Green1,
- Paresh Vyas1 and
- Catherine Porcher1,3
- 1MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DS, United Kingdom;
- 2Computational Biology Research Group (CBRG), Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford OX3 9DS, United Kingdom
Abstract
Coordination of cellular processes through the establishment of tissue-specific gene expression programs is essential for lineage maturation. The basic helix-loop-helix hemopoietic transcriptional regulator TAL1 (formerly SCL) is required for terminal differentiation of red blood cells. To gain insight into TAL1 function and mechanisms of action in erythropoiesis, we performed ChIP-sequencing and gene expression analyses from primary fetal liver erythroid cells. We show that TAL1 coordinates expression of genes in most known red cell–specific processes. The majority of TAL1's genomic targets require direct DNA-binding activity. However, one-fifth of TAL1's target sequences, mainly among those showing high affinity for TAL1, can recruit the factor independently of its DNA binding activity. An unbiased DNA motif search of sequences bound by TAL1 identified CAGNTG as TAL1-preferred E-box motif in erythroid cells. Novel motifs were also characterized that may help distinguish activated from repressed genes and suggest a new mechanism by which TAL1 may be recruited to DNA. Finally, analysis of recruitment of GATA1, a protein partner of TAL1, to sequences occupied by TAL1 suggests that TAL1's binding is necessary prior or simultaneous to that of GATA1. This work provides the framework to study regulatory networks leading to erythroid terminal maturation and to model mechanisms of action of tissue-specific transcription factors.
Footnotes
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↵3 Corresponding author.
E-mail catherine.porcher{at}imm.ox.ac.uk; fax 44-1865-222-500.
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[Supplemental material is available online at http://www.genome.org. The ChIP-seq and expression array data from this study have been submitted to the NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession nos. GSE18720 and GSE21877, respectively. Processed data is also available at https://gbrowse.molbiol.ox.ac.uk/cgi-bin/gbrowse/SCLtargets/.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.104935.110.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
