A Cornucopia of Advances in Human Epigenomics

In 21 papers published this week across Cell Press journals, including 5 in this issue of Cell, the International Human Epigenome Consortium (IHEC) pushes forward our understanding of nucleosome positioning and modifications to DNA and histones in primary human cells. Collectively, these papers illuminate how changes to chromatin contribute to cell-type-specific biology, development, variation between individuals, and disease. The editors of Cell Press are pleased to present these papers to readers in a unified way. The insights and impact of the collection of papers are truly more than the sum of the individual parts, and we hope that contemporaneous publication facilitates appreciation of the synergies between the different comprehensive datasets, innovative methodological approaches, and rich biological observations. While the papers treat a relatively broad range of topics in terms of biological processes, diseases, and tissues, conceptually they converge on several themes highlighting how epigenomics research is forging ahead to provide us with a deeper understanding of what all these ‘‘marks’’ and their positions in a genome really mean. To begin with, while the ability to determine the genetic sequence of single cells was a sterling accomplishment, achieving single-cell resolution for epigenomic data presents different and, in many ways, greater challenges. Several of the IHEC papers make significant progress in this area by presenting approaches and high-resolution data that disentangle heterogeneity both within different cell types of a tissue and between regulatory elements in a clonal population of cells. Next, an important aim of collecting and analyzing epigenome data is to reveal aspects of the underlying biology and its relevant molecular mechanisms. A set of papers in the IHEC collection capitalize on epigenomic analysis combined with other datasets to identify transcription factors that play key roles in cell fate determination and oncogenesis. In a different twist, and underscoring the potential clinical relevance of this kind of integrative analysis, a pair of papers reveals the role of certain metabolites and pathogen cues in eliciting epigenetic changes in the context of an immune response. One of these cues was indeed shown to boost the innate immune response. Still other papers in the package tackle the challenge of pinning down the effects of noncoding variants identified in genome-wide association studies. Do they affect gene expres-