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Pioneering the Nexus of Chromatin and Metabolism

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Front. Genet. | doi: 10.3389/fgene.2018.00578

Elucidating the role of chromatin state and transcription factors on the regulation of the Yeast Metabolic Cycle: a multi-omic integrative approach

 Victor Sánchez-Gaya1,  Salvador Casaní Galdón2, Manuel Ugidos1, Zheng Kuang3,  Jane Mellor4, Ana Conesa2, 5, 6 and  Sonia Tarazona1, 7*
  • 1Genomics of Gene Expression Laboratory, Centro de Investigacion Principe Felipe (CIPF), Spain
  • 2BioBam Bioinformatics S.L., Spain
  • 3Institute for System Genetics, School of Medicine, New York University, United States
  • 4Department of Biochemistry, Medical Sciences Division, University of Oxford, United Kingdom
  • 5Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, United States
  • 6Genetic Institute, University of Florida, United States
  • 7Applied Statistics, Operational Research and Quality Department, Universitat Politècnica de València, Spain

The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60\% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assess the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2 and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyl transferases.

Keywords: YMC, Histone Modifications, Gene Expression, Omics integration, Regression Models

Received: 03 Sep 2018; Accepted: 08 Nov 2018.

Edited by:

Trygve Tollefsbol, University of Alabama at Birmingham, United States

Reviewed by:

Valentina Tosato, AREA Science Park, Italy
Eulàlia De Nadal, Universidad Pompeu Fabra, Spain
Milena Georgieva, Bulgarian Academy of Sciences (BAS), Bulgaria  

Copyright: © 2018 Sánchez-Gaya, Casaní Galdón, Ugidos, Kuang, Mellor, Conesa and Tarazona. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sonia Tarazona, Centro de Investigacion Principe Felipe (CIPF), Genomics of Gene Expression Laboratory, Valencia, 46012, Spain,