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Nucleic Acids Res. 2012 Jan;40(2):553-68. doi: 10.1093/nar/gkr752. Epub 2011 Sep 16.

Modeling the relative relationship of transcription factor binding and histone modifications to gene expression levels in mouse embryonic stem cells.

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Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.


Transcription factor (TF) binding and histone modification (HM) are important for the precise control of gene expression. Hence, we constructed statistical models to relate these to gene expression levels in mouse embryonic stem cells. While both TF binding and HMs are highly 'predictive' of gene expression levels (in a statistical, but perhaps not strictly mechanistic, sense), we find they show distinct differences in the spatial patterning of their predictive strength: TF binding achieved the highest predictive power in a small DNA region centered at the transcription start sites of genes, while the HMs exhibited high predictive powers across a wide region around genes. Intriguingly, our results suggest that TF binding and HMs are redundant in strict statistical sense for predicting gene expression. We also show that our TF and HM models are cell line specific; specifically, TF binding and HM are more predictive of gene expression in the same cell line, and the differential gene expression between cell lines is predictable by differential HMs. Finally, we found that the models trained solely on protein-coding genes are predictive of expression levels of microRNAs, suggesting that their regulation by TFs and HMs may share a similar mechanism to that for protein-coding genes.

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