The genetic architecture of cell-type-specific cis-regulation [RNA-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Zea mays
PROVIDER: GSE275409 | GEO | 2024/11/19
REPOSITORIES: GEO
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Project description:Gene expression and complex phenotypes are determined by the activity of cis-regulatory elements. However, an understanding of how extant genetic variants affect cis-regulatory activity remains limited. Here, we investigated the consequences of cis-regulatory diversity using single-cell genomics of >0.7 million nuclei across 172 maize inbreds. Our analyses pinpointed cis-regulatory elements distinct to domesticated maize and how transposons rewired the regulatory landscape. We found widespread chromatin accessibility variation associated with >4.6 million genetic variants with largely cell-type-specific effects. Variants in TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR binding sites were the most prevalent determinants of chromatin accessibility. Finally, integration of genetic variants associated with chromatin accessibility, organismal trait variation, and population differentiation revealed how local adaptation has rewired regulatory networks in unique cellular context to alter maize flowering phenotypes.
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Project description:Methylation of chromosomal DNA in animals and plants is a fundamental mechanism of epigenetic regulation, and the maize genome, with its diverse complement of transposons and repeats, is a paradigm for transgenerational mechanisms such as paramutation and imprinting. We have determined the genome-wide cytosine methylation map of two maize inbred lines, B73 and Mo17, at high coverage and at single nucleotide resolution. Transposon methylation is highest in CG (65%) and CHG (50%) contexts (where H = A, C or T), while methylation in CHH (5%) contexts is guided by 24nt small interfering RNA (siRNA), and not by 21-22nt siRNA. We have found that CG (8%) methylation seems to deter insertion of Mutator transposons into exons, while CHH and CHG methylation at splice donor and acceptor sites strongly inhibits RNA splicing. Methylation differences between parents are inherited in recombinant inbred lines, but methylation switches, guided by siRNA, are widespread and persist for up to 8 generations. These differences influence splicing, and recurrent switching suggest that paramutation is much more common than previously supposed, and may contribute to heterosis. Our results provide a comprehensive high resolution resource for maize genome methylation, as well as a map of recurrent transgenerational epigenetic shifts (paramutation) in the two most commonly used inbred maize lines.
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Project description:Methylation of chromosomal DNA in animals and plants is a fundamental mechanism of epigenetic regulation, and the maize genome, with its diverse complement of transposons and repeats, is a paradigm for transgenerational mechanisms such as paramutation and imprinting. We have determined the genome-wide cytosine methylation map of two maize inbred lines, B73 and Mo17, at high coverage and at single nucleotide resolution. Transposon methylation is highest in CG (65%) and CHG (50%) contexts (where H = A, C or T), while methylation in CHH (5%) contexts is guided by 24nt small interfering RNA (siRNA), and not by 21-22nt siRNA. We have found that CG (8%) methylation seems to deter insertion of Mutator transposons into exons, while CHH and CHG methylation at splice donor and acceptor sites strongly inhibits RNA splicing. Methylation differences between parents are inherited in recombinant inbred lines, but methylation switches, guided by siRNA, are widespread and persist for up to 8 generations. These differences influence splicing, and recurrent switching suggest that paramutation is much more common than previously supposed, and may contribute to heterosis. Our results provide a comprehensive high resolution resource for maize genome methylation, as well as a map of recurrent transgenerational epigenetic shifts (paramutation) in the two most commonly used inbred maize lines. Genome-wide cytosine methylation map in 2 maize strains by bisulfite sequencing, and RNA and small RNA profiles in the same tissue using Illumina platform.
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Project description:RNA-directed DNA methylation (RdDM) in plants is a well-characterized example of RNA interference-related transcriptional gene silencing. To determine the relationships between RdDM and heterochromatin in the repeat-rich maize (Zea mays) genome, we performed whole-genome analyses of several heterochromatic features: dimethylation of lysine 9 and lysine 27 (H3K9me2 and H3K27me2), chromatin accessibility, DNA methylation, and small RNAs; we also analyzed two mutants that affect these processes, mediator of paramutation1 and zea methyltransferase2.
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Project description:Chromatin accessibility is an important functional genomics phenotype that influences transcription factor binding and gene expression. Genome-scale technologies allow chromatin accessibility to be mapped with high-resolution, facilitating detailed analyses into the genetic architecture and evolution of chromatin structure within and between species. We performed Formaldehyde-Assisted Isolation of Regulatory Elements sequencing (FAIRE-Seq) to map chromatin accessibility in two parental haploid yeast species, Saccharomyces cerevisiae and Saccharomyces paradoxus and their diploid hybrid. We show that although broad-scale characteristics of the chromatin landscape are well conserved between these species, accessibility is significantly different for 947 regions upstream of genes that are enriched for GO terms such as intracellular transport and protein localization exhibit. We also develop new statistical methods to investigate the genetic architecture of variation in chromatin accessibility between species, and find that cis effects are more common and of greater magnitude than trans effects. Interestingly, we find that cis and trans effects at individual genes are often negatively correlated, suggesting widespread compensatory evolution to stabilize levels of chromatin accessibility. Finally, we demonstrate that the relationship between chromatin accessibility and gene expression levels is complex, and a significant proportion of differences in chromatin accessibility might be functionally benign. There are 20 samples in total. These consist of 10 FAIRE-seq samples, specifically 6 haploid samples, S. cerevisiae strain UWOPS05_217_3 replicates 1 and 2, S. cerevisiae strain DBVPG1373 replicates 1 and 2, and S. paradoxus strain CBS432 replicates 1 and 2. There are also 4 diploid hybrid samples, hybrid between S. cerevisiae strain UWOPS05_217_3 and S. paradoxus strain CBS432 replicates 1 and 2, and the hybrid between S. cerevisiae strain DBVPG1373 and S. paradoxus strain CBS432 replicates 1 and 2. There are also RNA-seq samples for each of these 10 samples.
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