DESCRIPTION

Enhancer RNA prediction by integrating epigenetic and expression information

Supervisors: Anagha Joshi and David Hume

Funding: This project is eligible for a Roslin Institute, R(D)SVS 3year PhD studentship

The Enhancers RNAs (eRNAs) are produced from enhancers of highly active genes in a cell type specific manner. FANTOM5 consortium has generated deepCAGE time series datasets measuring the activity of promoters and enhancers from 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli1. Using this data, it has been shown that enhancer regions can be predicted using bi-directional expression as a proxy2. As not all enhancers show a bi-directional expression, this data provides a unique opportunity to investigate the directionality of the eRNA expression. The transcription at promoters is by default uni-directional3, whether this extends to eRNAs is still unclear. The aim of this project is to integrate expression data with epigenetic modifications (H3K4me1 & H3K27ac) to first group enhancers in three groups – bi-directional, uni-directional and not expressed using deepCAGE data. The next step is to characterise sequence and/or chromatin features associated with eRNA expression and their directionality. Specific sequence and epigenetic features distinguishing the three groups will be identified by collecting ChIP sequencing data for chromatin modifications at enhancers from the ENCODE resource. Identified features will be combined into a classifier to predict enhancer expression from its surrounding sequence and epigenetic signatures.

Intended Outcomes:

New way of integrating expression and epigenetic data
eRNA prediction across human cell types
Identification of features associated with eRNA directionality

References:
1.Arner, E., Daub, C.O., Vitting-Seerup, K., Andersson, R., Lilje, B., Drabløs, F., Lennartsson, A., Rönnerblad, M., Hrydziuszko, O., Vitezic, M., et al. Gene regulation. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347, 10101014 (2015).
2.Andersson, R., Gebhard, C., Miguel-Escalada, I., Hoof, I., Bornholdt, J., Boyd, M., Chen, Y., Zhao, X., Schmidl, C., Suzuki, T., et al An atlas of active enhancers across human cell types and tissues. Nature 507, 455461 (2014).
3.Duttke, S.H.C., Lacadie, S.A., Ibrahim, M.M., Glass, C.K., Corcoran, D.L., Benner, C., Heinz, S., Kadonaga, J.T., and Ohler, U. Human Promoters Are Intrinsically Directional. Mol. Cell 57, 674684 (2015).

HOW TO APPLY

Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be sent to: Liz Archibald, The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG or emailed to RDSVS.PGR.Admin[at]ed.ac.uk.

When applying for the studentship please state clearly the title of the studentship and the supervisor/s in your covering letter.

All applicants should also apply through the University's on-line application system for September 2016 entry via http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=829

International students should also apply for an Edinburgh Global Research Studentship (http://www.ed.ac.uk/schools-departments/student-funding/postgraduate/international/global/research).

DESCRIPTION

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