Abstract
We demonstrate that the binding sites for highly conserved transcription factors vary extensively between human and mouse. We mapped the binding of four tissue-specific transcription factors (FOXA2, HNF1A, HNF4A and HNF6) to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, from 41% to 89% of their binding events seem to be species specific. When the same protein binds the promoters of orthologous genes, approximately two-thirds of the binding sites do not align.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Conserved Sequence / genetics*
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Gene Expression Regulation*
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Genetic Variation
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Hepatocyte Nuclear Factor 1-alpha / genetics
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Hepatocyte Nuclear Factor 3-beta / genetics
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Hepatocyte Nuclear Factor 4 / genetics
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Hepatocyte Nuclear Factor 6 / genetics
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Humans
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Mice
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Regulatory Sequences, Nucleic Acid*
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Sequence Homology
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Transcription Factors / genetics*
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Transcription, Genetic*
Substances
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FOXA2 protein, human
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Foxa2 protein, mouse
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HNF1A protein, human
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HNF4A protein, human
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Hepatocyte Nuclear Factor 1-alpha
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Hepatocyte Nuclear Factor 4
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Hepatocyte Nuclear Factor 6
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Hnf1a protein, mouse
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Hnf4a protein, mouse
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Transcription Factors
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Hepatocyte Nuclear Factor 3-beta