Nearly all cells of an organism share the same genome but exhibit diverse phenotypes and carry out dramatically different functions. In eukaryotic cells the genome is organized into chromatin. Cell-type specific chromatin organization enables differential access and activity of regulatory elements and the manifestation of unique cellular phenotypes [1, 2]. Recent genome-wide studies have shown that cooperative chromatin modifications affect the structure of chromatin, shape the macro-environment of DNA, and add an extra layer of information to the genome sequence [3, 4]. These chromatin states are distinctive for different developmental stages [5], tissues [6], and disease states [7, 8], which can play important roles in establishing cell identity during development [9]. Therefore, studying histone modification states of multiple developmental stages and cell types may extend the knowledge of epigenetic dynamics and regulatory mechanisms in cellular differentiation, reprogramming, and disease processes.
Large-scale mapping of histone modifications has emerged as a powerful means for characterizing chromatin structures. The technology of chromatin immunoprecipitation followed by sequencing (Chip-Seq) can interrogate chromatin structure across the genome [10], which is increasingly applied for charting genome-wide maps of histone modifications [11, 12]. Currently, a large collection of histone modification maps are being generated for diverse developmental stages, lineages and tissues, with the emphasis on mammalian models [5, 13–17]. The expanding body of epigenomic data provides an opportunity to elucidate novel relationships among various histone modifications [18, 19], to characterize regulatory elements in the human genome [20], and to understand how global features of histone modifications impact cellular phenotypes across different developmental stages, lineages, and environmental conditions [21, 22].
Bearing these promises, a fundamental problem is to integrate histone modification maps of diverse developmental stages and tissues in the public domain. Over the past years, a few epigenomic databases have been developed for the integration of various human epigenomic data from different tissues and experiments [23–25]. These widely used databases are designed to catalyze basic biology and disease-oriented research, and mainly provide researchers with a resource for visualizing and downloading whole-genome datasets. However, it is not intuitive and easy to conduct detailed queries and comparisons for specific histone modification states of interested genomic regions. Another human histone modification database HHMD [26] includes only epigenomic data of several cell types, rather than integrate histone modification data from multiple developmental stages. Obviously, there is an urgent need to construct a specialized database that comprehensively provides high-resolution genome-wide histone modification data for epigenetic and developmental studies.
Here, we report a database iHMS that integrates human histone modification data covering diverse developmental stages and primary tissues. It also includes genome-wide expression data of different conditions and reference genes, GC content and CpG island information. iHMS has an intuitive and user-friendly query interface, which enables both basic and advanced search based on gene names/genomic region locations, histone modification marks and cell types, as three major query options. Moreover, it allows users to visualize and compare multiple genome-wide histone modification maps and related expression profiles at different developmental stages and tissues via a powerful browser. Thus, iHMS can provide a systematic view of the dynamic histone modification landscapes during cellular differentiation and development, which is useful for researchers to compare the variability of histone modification states with underlying gene expression, to identify cell-type-specific histone modification states and their regulatory implications for cellular phenotypes across different developmental stages and tissues.