TY - JOUR
T1 - Elucidating the Role of Chromatin State and Transcription Factors on the Regulation of the Yeast Metabolic Cycle
T2 - A Multi-Omic Integrative Approach
AU - Sánchez-Gaya, Víctor
AU - Casaní-Galdón, Salvador
AU - Ugidos, Manuel
AU - Kuang, Zheng
AU - Mellor, Jane
AU - Conesa, Ana
AU - Tarazona, Sonia
N1 - Funding Information:
We are grateful to Jef Boeke and Benjamin Tu for providing data from the histone modification H3K18ac. Funding. This work has received funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No 675610, from Generalitat Valenciana under the grant PROMETEO/2016/023 and from BBSRC (Biotechnology and Biological Sciences Research Council) BB/P00296X/1.
Publisher Copyright:
© Copyright © 2018 Sánchez-Gaya, Casaní-Galdón, Ugidos, Kuang, Mellor, Conesa and Tarazona.
PY - 2018/11/30
Y1 - 2018/11/30
N2 - 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 assessed 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 acetyltransferases.
AB - 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 assessed 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 acetyltransferases.
KW - YMC
KW - gene expression
KW - histone modifications
KW - omics integration
KW - regression
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U2 - 10.3389/fgene.2018.00578
DO - 10.3389/fgene.2018.00578
M3 - Article
C2 - 30555512
AN - SCOPUS:85077302227
SN - 1664-8021
VL - 9
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 578
ER -