The nature of developmental longitudinal trajectories of IgE responses differed between grass and mite allergen components, with temporal differences (early vs late onset) dominant in grass and diverging patterns of IgE responses (group 1 allergens, group 2 allergens, or both) in mite. Different longitudinal patterns bear different associations with clinical outcomes, which varied by allergen.

Gene expression in higher organisms is thought to be regulated by a complex network of transcription factor binding and chromatin modifications, yet the relative importance of these two factors remains a matter of debate. Here, we show that a computational approach allows surprisingly accurate prediction of histone modifications solely from knowledge of transcription factor binding both at promoters and at potential distal regulatory elements. This accuracy significantly and substantially exceeds what could be achieved by using DNA sequence as an input feature. Remarkably, we show that transcription factor binding enables strikingly accurate predictions across different cell lines. Analysis of the relative importance of specific transcription factors as predictors of specific histone marks recapitulated known interactions between transcription factors and histone modifiers. Our results demonstrate that reported associations between histone marks and gene expression may be indirect effects caused by interactions between transcription factors and histone-modifying complexes.epigenetics | gene regulation G ene expression is the fundamental process through which genetic information is dynamically and specifically deployed within cells. It is, therefore, of vital importance to all organisms and tightly controlled at both the transcriptional and posttranscriptional levels. Consequently, the elucidation of generegulatory mechanisms has been a central focus of biological research, with the area of transcriptional regulation having attracted intense attention over the last four decades.The canonical players in transcriptional regulation are sequence-specific DNA-binding transcription factors (TFs) that modulate gene expression by facilitating or inhibiting the recruitment of RNA polymerase to gene promoters (1). This paradigm has provided a powerful unifying mechanism for transcription, validated by a large amount of experimental evidence over the last five decades (see, e.g., ref. 2). Further evidence of the power of TFs to act as master regulators of gene expression and cell identity is illustrated by their ability to reprogram differentiated fibroblasts into embryonic stem (ES) cells (3).Research in the field of epigenetics has, however, suggested an alternative view that places posttranslational modifications of the histone subunits of nucleosomes in a central role of transcriptional regulation. The finding that particular combinations of histone modifications are associated with active and repressed gene promoters (4) has led to suggestions that a histone code controls gene expression (5, 6). Support for this hypothesis has come from the recent application of bioinformatic approaches to whole-genome measurements of both histone modifications and gene expression, which have demonstrated that gene expression can be predicted from histone modifications (7,8). This model has generated intense interest and is part of the stimulation behind the search for epigenetic causes of human disease (9).However, although histone mo...