PerspectiveGene Expression

Transcription factors read epigenetics

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Science  05 May 2017:
Vol. 356, Issue 6337, pp. 489-490
DOI: 10.1126/science.aan2927

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Summary

Decoding precisely how sequence-specific DNA binding proteins (called transcription factors) recognize, access, and act at their genomic binding sites is challenging. One shortcoming is the lack of knowledge about DNA binding specificities (motifs) for hundreds of the estimated ∼1600 human transcription factors. Another is how transcription factor binding is modulated by “epigenetics”—a contentious term that refers to heritable states of both cells and organisms, as well as the covalent chemical modifications of DNA and protein that often provide the underlying mechanism (1). DNA methylation at cytosine and guanine dinucleotides (mCG) satisfies most views of epigenetics, as it is inherited across cell divisions and functions in imprinting (parent-of-origin-dependent gene expression). On page 502 of this issue, Yin et al. (2) provide a comprehensive look at the extent to which human transcription factor binding is affected by mCG, and make a striking finding: Many homeodomain transcription factors—perhaps the best-characterized developmental regulators in biology (3)—can bind to specific methylated DNA sequences.