Publications by authors named "G D May"

689 Publications

Chromatin loop anchors contain core structural components of the gene expression machinery in maize.

BMC Genomics 2021 Jan 6;22(1):23. Epub 2021 Jan 6.

Corteva Agriscience, 8325 NW, 62nd Avenue, Johnston, Iowa, 50131, USA.

Background: Three-dimensional chromatin loop structures connect regulatory elements to their target genes in regions known as anchors. In complex plant genomes, such as maize, it has been proposed that loops span heterochromatic regions marked by higher repeat content, but little is known on their spatial organization and genome-wide occurrence in relation to transcriptional activity.

Results: Here, ultra-deep Hi-C sequencing of maize B73 leaf tissue was combined with gene expression and open chromatin sequencing for chromatin loop discovery and correlation with hierarchical topologically-associating domains (TADs) and transcriptional activity. A majority of all anchors are shared between multiple loops from previous public maize high-resolution interactome datasets, suggesting a highly dynamic environment, with a conserved set of anchors involved in multiple interaction networks. Chromatin loop interiors are marked by higher repeat contents than the anchors flanking them. A small fraction of high-resolution interaction anchors, fully embedded in larger chromatin loops, co-locate with active genes and putative protein-binding sites. Combinatorial analyses indicate that all anchors studied here co-locate with at least 81.5% of expressed genes and 74% of open chromatin regions. Approximately 38% of all Hi-C chromatin loops are fully embedded within hierarchical TAD-like domains, while the remaining ones share anchors with domain boundaries or with distinct domains. Those various loop types exhibit specific patterns of overlap for open chromatin regions and expressed genes, but no apparent pattern of gene expression. In addition, up to 63% of all unique variants derived from a prior public maize eQTL dataset overlap with Hi-C loop anchors. Anchor annotation suggests that < 7% of all loops detected here are potentially devoid of any genes or regulatory elements. The overall organization of chromatin loop anchors in the maize genome suggest a loop modeling system hypothesized to resemble phase separation of repeat-rich regions.

Conclusions: Sets of conserved chromatin loop anchors mapping to hierarchical domains contains core structural components of the gene expression machinery in maize. The data presented here will be a useful reference to further investigate their function in regard to the formation of transcriptional complexes and the regulation of transcriptional activity in the maize genome.
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http://dx.doi.org/10.1186/s12864-020-07324-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789236PMC
January 2021

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Mol Psychiatry 2020 Dec 7. Epub 2020 Dec 7.

Department of Psychiatry and Behavioral Health, Penn State College of Medicine, Hershey, PA, USA.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.
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http://dx.doi.org/10.1038/s41380-020-00967-1DOI Listing
December 2020

Mir142 loss unlocks IDH2-dependent leukemogenesis through antagonistic regulation of HOX genes.

Sci Rep 2020 11 10;10(1):19390. Epub 2020 Nov 10.

UCL Cancer Institute, University College London, London, UK.

AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2. Our analysis suggests that IDH2 is an incoherent oncogene, with both positive and negative impacts on leukemogenesis, which requires the action of cooperating mutations to alleviate repression of Hoxa genes in order to advance to leukemia. This model, therefore, provides a compelling rationale for understanding how different mutations cooperate to drive leukemogenesis and the context-dependent effects of oncogenic mutations.
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http://dx.doi.org/10.1038/s41598-020-76218-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656267PMC
November 2020

Habitat-scale heterogeneity maintains fungal endophyte diversity in two native prairie legumes.

Mycologia 2021 Jan-Feb;113(1):20-32. Epub 2020 Nov 4.

Department of Ecology, Evolution and Behavior, University of Minnesota , St. Paul, Minnesota 55108.

The assembly of fungal endophyte communities within plants depends on the complex interactions of fungal taxa, their host plants, and the abiotic environment. Prairie plant communities provide a unique avenue to explore the interplay of biotic and abiotic factors affecting endophyte communities, since the historical distribution of prairies spans a broad range of temperature and precipitation, while the distances between small fragments of contemporary prairie communities may challenge the dispersal capabilities of these otherwise ubiquitous fungi. We sampled foliar fungal endophytes from two native prairie legumes, purple and white prairie clovers ( and ), in 17 remnant prairie sites across Minnesota in order to evaluate the relative contributions of abiotic factors, host species, and dispersal limitation to the diversity and structure of these communities. We found that similarity of communities was significantly associated with their location along a temperature and precipitation gradient, and we showed a distance-decay relationship that suggests dispersal limitations only over very large spatial scales. Although the effect of host species was small relative to these other factors, the two species maintained distinct communities within sites where they co-occur. Our results illustrate the capacity of many of these endophyte taxa to disperse over large distances and across heterogeneous biotic and abiotic environments and suggest that the interplay of biotic and abiotic factors maintains high diversity observed in endophyte communities.
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http://dx.doi.org/10.1080/00275514.2020.1813487DOI Listing
November 2020