Cell lines were not tested for mycoplasma contamination. Commonly misidentified lines (See ICLAC register) No commonly misidentified cell lines were used.

Transcription factors are DNA-binding proteins that have key roles in gene regulation 1,2. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes 3-6. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) experiments using the human HepG2 cell line for 208 chromatinassociated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP-seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium. There are an estimated 1,639 transcription factors (TFs) in the human genome 2 , and up to 2,500 CAPs when we include transcriptional cofactors, RNA polymerase-associated proteins, histone-binding regulators, and chromatin-modifying enzymes 1,7. A typical TF binds to a short DNA sequence motif, and, in vivo, some TFs exhibit additional chromosomal occupancy mediated by their interactions with other CAPs 8-10. CAPs are vital for orchestrating cell type-and cell state-specific gene regulation, including the temporal coordination of gene expression in developmental processes, environmental responses, and disease states 3-6,11-13. Identifying genomic regions with which a TF is physically associated, referred to as TF binding sites (TFBSs), is an important step towards understanding its biological roles. The most common genome-wide assay for identifying TFBSs is ChIP-seq 14-16. In addition to highlighting potentially active regulatory DNA elements by direct measurement, ChIP-seq data can define DNA sequence motifs that can be used, often in conjunction with expression data and chromatin accessibility maps, to infer likely binding events in other cellular contexts without performing direct assays. Although motifs identified by ChIP-seq are often representative of direct binding, this is not always the case, as co-occurrence of other TFs could ...

ENCODE 3 (2012-2017) expanded production and added new types of assays 8 (Fig. 1, Extended Data Fig. 1), which revealed landscapes of RNA binding and the 3D organization of chromatin via methods such as chromatin interaction analysis by paired-end tagging (ChIA-PET) and Hi-C chromosome conformation capture. Phases 2 and 3 delivered 9,239 experiments (7,495 in human and 1,744 in mouse) in more than 500 cell types and tissues, including mapping of transcribed regions and transcript isoforms, regions of transcripts recognized by RNA-binding proteins, transcription factor binding regions, and regions that harbour specific histone modifications, open chromatin, and 3D chromatin interactions. The results of all of these experiments are available at the ENCODE portal (http://www.encodeproject.org). These efforts, combined with those of related projects and many other laboratories, have produced a greatly enhanced view of the human genome (Fig. 2), identifying 20,225 protein-coding and 37,595 noncoding genes