Identification of gene specific cis-regulatory elements during differentiation of mouse embryonic stem cells: An integrative approach using high-throughput datasets.

Autor: M S Vijayabaskar, Debbie K Goode, Nadine Obier, Monika Lichtinger, Amber M L Emmett, Fatin N Zainul Abidin, Nisar Shar, Rebecca Hannah, Salam A Assi, Michael Lie-A-Ling, Berthold Gottgens, Georges Lacaud, Valerie Kouskoff, Constanze Bonifer, David R Westhead
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Computational Biology, Vol 15, Iss 11, p e1007337 (2019)
Druh dokumentu: article
ISSN: 1553-734X
1553-7358
DOI: 10.1371/journal.pcbi.1007337
Popis: Gene expression governs cell fate, and is regulated via a complex interplay of transcription factors and molecules that change chromatin structure. Advances in sequencing-based assays have enabled investigation of these processes genome-wide, leading to large datasets that combine information on the dynamics of gene expression, transcription factor binding and chromatin structure as cells differentiate. While numerous studies focus on the effects of these features on broader gene regulation, less work has been done on the mechanisms of gene-specific transcriptional control. In this study, we have focussed on the latter by integrating gene expression data for the in vitro differentiation of murine ES cells to macrophages and cardiomyocytes, with dynamic data on chromatin structure, epigenetics and transcription factor binding. Combining a novel strategy to identify communities of related control elements with a penalized regression approach, we developed individual models to identify the potential control elements predictive of the expression of each gene. Our models were compared to an existing method and evaluated using the existing literature and new experimental data from embryonic stem cell differentiation reporter assays. Our method is able to identify transcriptional control elements in a gene specific manner that reflect known regulatory relationships and to generate useful hypotheses for further testing.
Databáze: Directory of Open Access Journals
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