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Session 6. Genomics and Epigenomics Lectures L6.1 L6.2

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Session 6. Genomics and Epigenomics Lectures L6.1 L6.2 Session 6. Genomics and Epigenomics Lectures L6.2 L6.1 Epigenetic mechanisms behind plant phenotypic plasticity Search for genetic variants Kinga Rutowicz1, Marcin Puzio2, Joanna Halibart- influencing cardiac hypertrophy — an Puzio1, Maciej Lirski1, Maciej Kotliński1,2, Magdalena integrative genomics approach A. Kroteń3, Lukasz Knizewski4, Bartosz Lange2, Anna Muszewska1,4, Katarzyna Śniegowska-Świerk5, Janusz Grzegorz Placha Kościelniak5, Roksana Iwanicka-Nowicka1,2, Krisztián Department of Internal Medicine, Hypertension and Vascular Diseases, Buza6, Franciszek Janowiak7, Katarzyna Żmuda5, Indrek The Medical University of Warsaw, Warsaw, Poland Jõesaar8, Katarzyna Laskowska-Kaszub2, Anna Fogtman1, e-mail: Grzegorz Placha <[email protected]> Hannes Kollist8, Piotr Zielenkiewicz1, Jerzy Tiuryn6, Paweł Siedlecki1,2, Szymon Swiezewski1, Krzysztof The left ventricular hypertrophy which is commonly ob- Ginalski4, Marta Koblowska1,2, Rafał Archacki2, Bartek served in aortic stenosis develops as an adaptive response Wilczynski6, Marcin Rapacz5, Andrzej Jerzmanowski1,2 to pressure overload and itself is an independent major risk factor for morbidity and mortality. Previous studies have 1Institute of Biochemistry and Biophysics, Polish Academy of Sciences, demonstrated a poor correlation between the degree of Warsaw, Poland; 2Laboratory of Systems Biology, University of Warsaw, Warsaw, Poland; 3College of Inter-Faculty Individual Studies aortic stenosis or other clinical factors and the degree of in Mathematics and Natural Sciences, University of Warsaw, Warsaw, left ventricular hypertrophy. The absence of a clear rela- Poland; 4Laboratory of Bioinformatics and Systems Biology, CeNT, tion between the stenosis-dependent pressure load on the University of Warsaw, Warsaw, Poland; 5Department of Plant Physiology, degree of left ventricular hypertrophy suggests that the University of Agriculture in Cracow, Kraków, Poland; 6Institute of Informatics, University of Warsaw, Warsaw, Poland; 7Institute of left ventricular phenotype is dependent on a polygenic Plant Physiology, Polish Academy of Sciences, Poland; 8Institute of background. Familial predisposition of left ventricular hy- Technology, University of Tartu, Estonia pertrophy is supported by several studies. In a recent ge- e-mail: Andrzej Jerzmanowski <[email protected]> nome-wide association study (GWAS) we found evidence for association between variation in left ventricular mass Plants are sessile organisms that complete their life cycles index and several chromosomal regions. We postulate that at the same location in which they grew from seeds. This these chromosomal regions harbor genes that contribute requires the ability to constantly adapt to a changing local to the development of heart hypertrophy in individuals environment as well as to interact in both a negative (com- with aortic stenosis. In this project we use an integrative petition) and a positive (cooperation) way with other plants genomics approach that combines GWAS results and in- populating the area, in order to optimize access to basic re- formative SNP linkage disequilibrium maps with transcrip- sources (light, water, mineral nutrients). These needs have tome sequencing data to identify novel genes and biological fostered – especially in angiosperm plants – the evolution pathways affecting cardiac hypertrophy that could not be of remarkable adaptive phenotypic plasticity and interactive identified using GWAS alone. capabilities. In response to the prevailing environmental con- ditions, a single plant genome is capable of generating a wide range of physiological and developmental phenotypes and supporting both competitive and cooperative (facilitative) interactions within plant communities. Phenotypic plasticity and cooperation enabled by facilitative interactions among plants have profound implications for plant evolution and are the subject of intensive study by theoretical and evolu- tionary plant ecologists. However, the mechanisms by which environmental conditions are communicated to the genome and affect transcription, enabling adaptive responses, are poorly understood. In particular, despite increasing evidence of the importance of epigenetic mechanisms in the dynamic interplay between environment and genomes underpinning adaptive plasticity, the link between these mechanisms and external cues remains enigmatic. We assessed the develop- mental, physiological and molecular role of the ‘stress in- ducible’ linker histone H1.3 in the adaptation of Arabidopsis thaliana to combined light limitation and drought and present evidence that H1.3, a member of a subfamily of plant H1 histones conserved in angiosperms but absent in mosses, ferns and gymnosperms, plays a key role in the Arabidopsis response to complex abiotic stresses. Our results give strong support to a notion that structural and cis-regulatory subfunc- tionalization that led to the evolution of ‘stress-inducible’ H1 variants may have helped to promote the rapid radiation of angiosperm plants on Earth. BIO2014 Congress Session 6. Genomics and Epigenomics 117 L6.3 Oral presentations Computing local chromatin state: O6.1 a supervised approach Bartek Wilczyński TCGA-based analysis of gliomas uncovers a putative role of miRNA-155 Institute of Informatics, University of Warsaw, Warsaw, Poland e-mail: Bartek Wilczyński <[email protected]> in regulation of gene expression It is now well established that local changes in the state Bartosz Wojtas, Bozena Kaminska-Kaczmarek of the chromatin fibre are essential for establishment of Laboratory of Molecular Neurobiology, Neurobiology Center, Nencki proper epigenetic changes in development. In particular, Institute of Experimental Biology, Warsaw, Poland changes in gene regulation require complex modifications e-mail: Bartosz Wojtas <[email protected]> of histone tails to be orchestrated both at the transcribed parts of chromosomes as well as in non-coding regula- Introduction: Molecular mechanisms of progression from tory regions. Given the abundance of data on both his- lower grade gliomas to anaplastic, highly malignant forms tone modifications and histone modifying enzymes from are poorly known. The Cancer Genome Atlas (TCGA) ChIP-Seq or similar experiments it is now a good time to project provides an opportunity to study molecular aspects ask if or how well can we predict the function of regula- of transcription regulation among histological subtypes of tory elements such as enhancers or insulators on a genomic gliomas in large patient cohorts. scale. In this talk I will present our recent results regard- Materials and Methods: In a present study both mRNA ing prediction of regulatory elements using data from EN- and miRNA expression datasets from histological subtypes CODE and modENCODE projects to discover positions of WHO II and III grade gliomas were acquired from of enhancer and isulator elements in fruitfly and human the TCGA website. It includes next generation sequenc- genomes. ing data for mRNA and miRNA for 54 astrocytoma, 53 oligodendroglioma and 37 oligoastrocytoma tumors. Many miRNAs were associated with differential gene expression in gliomas, threfore miRNA and mRNA expression was analyzed to find relationship between a level of specific miRNA and regulation of gene expression. Best inverse correlations for astrocytomas (rho < -0.5 and Bonferroni corrected p-value 0.1) were identified and 4 algorithms (miRDB, microT4-CDS, Paccmit, Paccmit-CDS) were used for bioinformatics prediction of the possible target genes of miRNAs. Correlations confirmed by 2 out of 4 algo- rithms were reported. GSEA (gene set enrichment analysis) of Gene Ontology terms for biological function and CGP (chemical and genetic perturbations) enrichment was per- formed to investigate genes that were potentially regulated by miRNAs in gliomas. Results: An integrated analysis of the observed miRNAs and mRNAs resulted in 100 highly correlated miRNA-mR- NA pairs that fulfilled criteria of analysis. Strikingly 60% of them were putative regulations of miRNA-155, which is a very well known oncomir involved in glioblastoma de- velopment. GSEA analysis of putative targets of miRNA in astrocytoma revealed that amongst most enriched GO terms for biological functions ESTABLISHMENT AND OR MAINTENANCE OF CHROMATIN ARCHITEC- TURE and CHROMOSOME ORGANIZATION AND BIOGENESIS were most enriched functional groups. The most GSEA CGP enriched group consisted genes cor- related with a proneural type of glioblastoma multiforme (WHO grade IV). Conclusions: MiRNA-155 could be a key player in astro- cytoma development. Main functional groups of miRNA targets are genes involved in chromosome organization and chromatin architecture. The expression pattern of genes that are putative targets of miRNA in astrocytoma is very similar to the expression patterns of the proneural type of glioblastoma multiforme. Acknowledgements Work is supported by 2012/04/A/NZ3/00630 grant from National Sci- ence Centre. Warsaw, September 9th–12th 2014 118 Session 6. Genomics and Epigenomics O6.2 O6.3 The extent of gene copy number Hybrid nature of pathogenic fungi variation in natural populations Leszek P. Pryszcz1,2, Tibor Németh3, Attila of Arabidopsis thaliana Gácser3, Toni Gabaldón1,2,4 1,2 2 Agnieszka Żmieńko , Anna Samelak-Czajka , Małgorzata 1Bioinformatics and Genomics Programme, Centre for Genomic Marcinkowska-Swojak1, Maciej Szymański3, Wojciech Regulation (CRG), Barcelona, Spain; 2Universitat Pompeu Fabra (UPF). M. Karłowski3, Piotr Kozłowski1,
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