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Sci Rep. 2017 Jul 18;7(1):5776. doi: 10.1038/s41598-017-06200-4.

Associating transcription factors and conserved RNA structures with gene regulation in the human brain.

Author information

1
Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
2
Department of Veterinary and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark.
3
Max-Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307, Dresden, Germany.
4
Max-Planck Institute for the Physics of Complex Systems, Nöthnitzer Str. 38, 01187, Dresden, Germany.
5
Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
6
Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. ruzzo@cs.washington.edu.
7
Paul G. Allen School of Computer Science & Engineering, and Department of Genome Sciences, University of Washington, 185 Stevens Way, WA, 98195-2350, Seattle, USA. ruzzo@cs.washington.edu.
8
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., WA, 98109, Seattle, USA. ruzzo@cs.washington.edu.
9
Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. gorodkin@rth.dk.
10
Department of Veterinary and Animal Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark. gorodkin@rth.dk.

Abstract

Anatomical subdivisions of the human brain can be associated with different neuronal functions. This functional diversification is reflected by differences in gene expression. By analyzing post-mortem gene expression data from the Allen Brain Atlas, we investigated the impact of transcription factors (TF) and RNA secondary structures on the regulation of gene expression in the human brain. First, we modeled the expression of a gene as a linear combination of the expression of TFs. We devised an approach to select robust TF-gene interactions and to determine localized contributions to gene expression of TFs. Among the TFs with the most localized contributions, we identified EZH2 in the cerebellum, NR3C1 in the cerebral cortex and SRF in the basal forebrain. Our results suggest that EZH2 is involved in regulating ZIC2 and SHANK1 which have been linked to neurological diseases such as autism spectrum disorder. Second, we associated enriched regulatory elements inside differentially expressed mRNAs with RNA secondary structure motifs. We found a group of purine-uracil repeat RNA secondary structure motifs plus other motifs in neuron related genes such as ACSL4 and ERLIN2.

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