ASMdb: a comprehensive database for allele-specific DNA methylation in diverse organisms

Zhou, Qiangwei; Guan, Pengpeng; Zhu, Zhixian; Cheng, Shuiyuan; Zhou, Cong; Wang, Huanhuan; Xu, Qian; Sung, Wing‐Kin; Li, Guo Liang

doi:10.1093/nar/gkab937

Cited by 21 publications

(19 citation statements)

References 56 publications

(51 reference statements)

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“…Increased methylation of MITEs, located upstream or downstream of a coding region, can also repress or activate gene expression (Xu et al ., 2020). In this study, based on the methylation data from the Allele‐Specific DNA Methylation Database (ASMdb; Zhou et al ., 2022), we found that the MITE region of the HTG3 promoter was hypermethylated compared with neighboring regions, suggesting that the suppression of HTG3a may be a result of increased DNA methylation in the promoter.…”

Section: Discussionmentioning

confidence: 79%

A MITE variation‐associated heat‐inducible isoform of a heat‐shock factor confers heat tolerance through regulation of JASMONATE ZIM‐DOMAIN genes in rice

Yao

Xiang

et al. 2022

New Phytologist

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High temperatures cause huge yield losses in rice. Heat-shock factors (Hsfs) are key transcription factors which regulate the expression of heat stress-responsive genes, but natural variation in and functional characterization of Hsfs have seldom been reported.A significant heat response locus was detected via a genome-wide association study (GWAS) using green leaf area as an indicative trait. A miniature inverted-repeat transposable element (MITE) in the promoter of a candidate gene, HTG3 (heat-tolerance gene on chromosome 3), was found to be significantly associated with heat-induced expression of HTG3 and heat tolerance (HT). The MITE-absent variant has been selected in heat-prone rice-growing regions.HTG3a is an alternatively spliced isoform encoding a functional Hsf, and experiments using overexpression and knockout rice lines showed that HTG3a positively regulates HT at both vegetative and reproductive stages. The HTG3-regulated genes were enriched for heat shock proteins and jasmonic acid signaling. Two heat-responsive JASMONATE ZIM-DOMAIN (JAZ) genes were confirmed to be directly upregulated by HTG3a, and one of them, OsJAZ9, positively regulates HT.We conclude that HTG3 plays an important role in HT through the regulation of JAZs and other heat-responsive genes. The MITE-absent allele may be valuable for HT breeding in rice.

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Section: Discussionmentioning

confidence: 79%

A MITE variation‐associated heat‐inducible isoform of a heat‐shock factor confers heat tolerance through regulation of JASMONATE ZIM‐DOMAIN genes in rice

Yao

Xiang

et al. 2022

New Phytologist

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“…The young group had 18 aDMRs and the adult group had 13 aDMRs. Previously, Zhou et al [ 24 ] reported 24,557 allele-specific expressed genes (ASEGs) of 91 human tissues and cell lines of the allele-specific DNA methylation database. Of these 24,557, five genes were shared with our 15 aDMR-related genes in the thymus, which were U6 , ZNF287 , PELO , ZNF596 and NUPR2 .…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus

Qiu

Fan

et al. 2022

IJMS

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We analyzed whole-genome bisulfite sequencing (WGBS) and RNA sequencing data of two young (1 year old) and two adult (9 years old) rhesus macaques (Macaca mulatta) to characterize the genomic DNA methylation profile of the thymus and explore the molecular mechanism of age-related changes in the thymus. Combining the two-omics data, we identified correlations between DNA methylation and gene expression and found that DNA methylation played an essential role in the functional changes of the aging thymus, especially in immunity and coagulation. The hypomethylation levels of C3 and C5AR2 and the hypermethylation level of C7 may lead to the high expressions of these genes in adult rhesus macaque thymuses, thus activating the classical complement pathway and the alternative pathway and enhancing their innate immune function. Adult thymuses had an enhanced coagulation pathway, which may have resulted from the hypomethylation and upregulated expressions of seven coagulation-promoting factor genes (F13A1, CLEC4D, CLEC4E, FCN3, PDGFRA, FGF2 and FGF7) and the hypomethylation and low expression of CPB2 to inhibit the degradation of blood clots. Furthermore, the functional decline in differentiation, activation and maturation of T cells in adult thymuses was also closely related to the changes in methylation levels and gene expression levels of T cell development genes (CD3G, GAD2, ADAMDEC1 and LCK) and the thymogenic hormone gene TMPO. A comparison of the age-related methylated genes among four mammal species revealed that most of the epigenetic clocks were species-specific. Furthermore, based on the genomic landscape of allele-specific DNA methylation, we identified several age-related clustered sequence-dependent allele-specific DNA methylated (cS-ASM) genes. Overall, these DNA methylation patterns may also help to assist with understanding the mechanisms of the aging thymus with the epigenome.

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“…Allele specific gene expression data for IMR-90 and H1-hESC were obtained from the UCSD Human Reference Epigenome Mapping Project (Kundaje et al ., 2015) via the ASMdb (Zhou et al ., 2022). Allele specific expression data for GM12878 were obtained from previously published work (see SI Table 2) (Workman et al ., 2019).…”

Section: Methodsmentioning

confidence: 99%

“…The filtered gene list was merged with Ensembl IDs from Gencode v38. ASEG data for IMR90 and H1-hESC were obtained from the UCSD Human Reference Epigenome Mapping Project (Kundaje et al, 2015) via the ASMdb (Zhou et al, 2022).…”

Section: Data Availabilitymentioning

confidence: 99%

Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters

Richer

Tian

Schoenfelder

et al. 2022

Preprint

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BackgroundThere is widespread interest in the three-dimensional chromatin conformation of the genome and its impact on gene expression. However, these studies frequently do not consider parent-of-origin differences, such as genomic imprinting, which result in monoallelic expression. In addition, genome-wide allele-specific chromatin conformation associations have not been extensively explored. There are few accessible bioinformatic workflows for investigating allelic conformation differences and these require pre-phased haplotypes which are not widely available.ResultsWe developed a bioinformatic pipeline, “HiCFlow”, which performs haplotype assembly and visualisation of parental chromatin architecture. We benchmarked the pipeline using prototype haplotype phased Hi-C data from GM12878 cells at three disease associated imprinted gene clusters. Using RC-HiC (Region Capture Hi-C) and Hi-C data from further human cell lines (1-7HB2, IMR-90, and H1-hESCs) we were able to robustly identify the known stable allele-specific interactions at the H19/IGF2 locus. Other imprinted loci (DLK1 and SNRPN) were more variable and there was no “canonical imprinted 3D structure”, but we could detect allele-specific differences in A/B compartmentalisation. Genome-wide, when TADs were unbiasedly ranked according to their allele-specific contact frequencies, a set of “allele-specific TADs” (ASTADs) could be defined. These occurred in genomic regions of high sequence variation. In addition to imprinted genes, ASTADs were also enriched for allele-specific expressed (ASE) genes. We found loci that have not previously been identified as ASE such as the bitter taste receptors (TAS2Rs).ConclusionsThis study highlights the widespread differences in chromatin conformation between heterozygous loci and provides a new framework for understanding ASE.

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ASMdb: a comprehensive database for allele-specific DNA methylation in diverse organisms

Cited by 21 publications

References 56 publications

A MITE variation‐associated heat‐inducible isoform of a heat‐shock factor confers heat tolerance through regulation of JASMONATE ZIM‐DOMAIN genes in rice

A MITE variation‐associated heat‐inducible isoform of a heat‐shock factor confers heat tolerance through regulation of JASMONATE ZIM‐DOMAIN genes in rice

Genome-Wide DNA Methylation Profile Indicates Potential Epigenetic Regulation of Aging in the Rhesus Macaque Thymus

Widespread allele-specific topological domains in the human genome are not confined to imprinted gene clusters

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