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Open Access Highly Accessed Research article

Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data

Yun Chen1, Mette Jørgensen1, Raivo Kolde23, Xiaobei Zhao1, Brian Parker1, Eivind Valen1, Jiayu Wen1 and Albin Sandelin1*

  • * Corresponding author: Albin Sandelin albin@binf.ku.dk

  • † Equal contributors

Author Affiliations

1 The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre, Copenhagen University, Ole Maaloes Vej 5, DK-2200 Denmark

2 Institute of Computer Science, University of Tartu, Liivi 2-314, 50409 Tartu, Estonia

3 Quretec, Ülikooli 6a, 51003 Tartu, Estonia

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BMC Genomics 2011, 12:544  doi:10.1186/1471-2164-12-544

Published: 3 November 2011

Abstract

Background

Initiation and elongation of RNA polymerase II (RNAPII) transcription is regulated by both DNA sequence and chromatin signals. Recent breakthroughs make it possible to measure the chromatin state and activity of core promoters genome-wide, but dedicated computational strategies are needed to progress from descriptive annotation of data to quantitative, predictive models.

Results

Here, we describe a computational framework which with high accuracy can predict the locations of core promoters, the amount of recruited RNAPII at the promoter, the amount of elongating RNAPII in the gene body, the mRNA production originating from the promoter and finally also the stalling characteristics of RNAPII by considering both quantitative and spatial features of histone modifications around the transcription start site (TSS).

As the model framework can also pinpoint the signals that are the most influential for prediction, it can be used to infer underlying regulatory biology. For example, we show that the H3K4 di- and tri- methylation signals are strongly predictive for promoter location while the acetylation marks H3K9 and H3K27 are highly important in estimating the promoter usage. All of these four marks are found to be necessary for recruitment of RNAPII but not sufficient for the elongation. We also show that the spatial distributions of histone marks are almost as predictive as the signal strength and that a set of histone marks immediately downstream of the TSS is highly predictive of RNAPII stalling.

Conclusions

In this study we introduce a general framework to accurately predict the level of RNAPII recruitment, elongation, stalling and mRNA expression from chromatin signals. The versatility of the method also makes it ideally suited to investigate other genomic data.