Chromatin states reveal functional associations for globally defined transcription start sites in four human cell lines.

Morten Rye,Geir Sandve,Piero Carninci,Hideya Kawaji,Finn Drabløs,Alistair Rr Forrest,Carsten O Daub

doi:10.1186/1471-2164-15-120

Abstract

BackgroundDeciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects.ResultsTranscription start sites can be distinguished by chromatin states defined by specific combinations of both chromatin mark enrichment and the profile shapes of these chromatin marks. The observed patterns can be associated with cellular functions and processes, and they also show association with expression level, location relative to nearby genes, and CpG content. In particular we find a substantial number of repressed inter- and intra-genic transcription start sites enriched for active chromatin marks and Pol II, and these sites are strongly associated with immediate-early response processes and cell signaling. Associations between start sites with similar chromatin patterns are validated by significant correlations in their global expression profiles.ConclusionsThe results confirm the link between chromatin state and cellular function for expressed transcripts, and also indicate that active chromatin states at repressed transcripts may poise transcripts for rapid activation during immune response.

Highlights

Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology
Most RTSSs are intra- or inter-genic, rather than being located at or close to currently annotated transcription start sites (TSSs). These RTSSs are mostly repressed in the four cell lines studied, we discovered a substantial number of such repressed inter- and intra-genic RTSSs harboring activating chromatin marks and polymerase II (Pol II), indicative of regulatory elements poised for transcription
Defined RTSSs are mostly located in intra- and intergenic regions, and repressed in individual cell lines We defined a set of 179 369 global RTSSs from the 184 827 RTSSs produced by the FANTOM5 consortium, and used this set throughout the rest of the study (Methods)

Summary

Introduction

Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes is an important task for improving our understanding of human cellular biology. We investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects. Deciphering the most common modes by which chromatin regulates transcription, and how this is related to cellular status and processes, represents an ongoing endeavor towards our understanding of human cellular biology. Among the several approaches taken by ENCODE to investigate the different aspects of transcript regulation, the mapping of chromatin modifications and transcription factor binding sites in selected human cell lines using ChIP-Seq [6,7] is probably the most comprehensive. To facilitate comparison and utilize the efforts made by both projects, the four cell lines K562, GM12878, HeLa-S3 and HepG2 used by ENCODE where subjected to CAGE in FANTOM5

Methods

Results

Discussion

Conclusion