Biology subjects

Thiel, J.

Publications and source records attributed to Thiel, J..

5 recordsLinked to original sources

bioRxiv2026

Programmed chromosome elimination correlates with the overexpression of cohesin and additional B chromosome-encoded genes in Aegilops speltoides

Programmed chromosome elimination is a highly controlled developmental process in which specific chromosomes are selectively lost from defined cell types during development. Despite its broad occurrence across plants and animals, the molecular mechanisms driving the tissue-specific elimination of chromosomes remain largely unresolved. Here, we exploit the root-specific elimination of supernumerary B chromosomes in Aegilops speltoides as a tractable model to identify the genetic basis of programmed chromosome loss. A high-quality, chromosome-scale genome assembly was generated, assigning 398 Mb of sequence to the Ae. speltoides B chromosome. Transcriptome profiling across seven tissue types representing chromosome elimination-active, elimination-negative, and B chromosome nondisjunction conditions identified 3,262 genes consistently upregulated in elimination-associated tissues, including 1,035 B genes. Stepwise subtraction of genes expressed in post-elimination and B chromosome-retaining reference tissues, followed by intersection with genes expressed during B nondisjunction in anthers, identified a candidate gene set enriched for chromosome segregation functions. From this set, we prioritized SYN2-B, a B chromosome-encoded cohesin -kleisin subunit whose Arabidopsis thaliana ortholog AtSYN2 induces chromosome bridges and micronucleus formation when misregulated. CENH3-B, an -type centromeric histone variant identified through GO enrichment analysis of B genes expressed in elimination-associated tissues, was shown to be incorporated in centromeres of both A and B chromosomes by transient gene expression assays using protoplasts and 3D structured illumination microscopy. These findings support a model in which B chromosome-encoded perturbations of cohesin activity and centromere composition contribute to selective B chromosome nondisjunction and their elimination in root tissues. Moreover, the SYN2-B promoter is enriched for ethylene response factor-binding sites compared to its A-encoded paralog, suggesting that ethylene is implicated in the root identity pathway driving root-specific B chromosome elimination.

genetics↗

bioRxiv2025

Sorghum embryos undergoing B chromosome elimination express B-variants of mitotic-related genes

BackgroundSelective DNA elimination occurs across diverse species and plays a crucial role in evolution and development. This process encompasses small deletions, complete removal of chromosomes, or even the elimination of entire parental genomes. Despite its importance, the molecular mechanisms governing selective DNA elimination remain poorly understood. Our study focused on the tissue-specific elimination of Sorghum purpureosericeum B chromosome(s) during embryo development. ResultsIn situ B chromosome visualisation, complemented by transcriptomic profiling and gene-enrichment analysis, allowed us to identify 28 candidate genes poten-tially linked to chromosome elimination. We show that elimination is a developmentally programmed process, peaking during mid-embryogenesis and nearly completed at later stages, leaving B chromosomes only in restricted meristematic regions. Genome sequencing revealed that the sorghum B chromosome is of multi-A chromosomal origin, has reduced gene density, is enriched in repetitive sequences, and carries a novel centromeric repeat (SpuCL166). Transcriptome analyses identified B-specific variants of kinetochore, cohesion, and checkpoint genes that are expressed during active elimination, while structural modeling of CENH3 and CENP-C indicated functional divergence at the kinetochore interface. ConclusionHere, we provide the first comprehensive genomic and transcriptomic characterization of B chromosome and its elimination in Sorghum purpureosericeum. Our findings suggest that B chromosomes express modified mitotic machinery to control their own fate. By establishing a framework of candidate genes, this study opens new avenues for dissecting the molecular mechanisms of chromosome elimination and provides a critical foundation for understanding how genomes evolve to regulate and tolerate supernumerary chromosomal elements.

plant biology↗

bioRxiv2025

KLF5 controls subtype-independent highly interactive enhancers in pancreatic cancer to regulate cell survival

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer with a 5-year survival rate of 13%. Despite recent molecular stratification of tumors into distinct classical and basal-like cell states, most tumors are heterogeneous contain of both subtypes. Therefore, therapeutic approaches targeting one subtype may not be suitable for PDAC therapy. Here, we integrated chromatin accessibility (ATAC-seq), genome-wide occupancy (ChIP-seq) for epigenetic status (H3K27ac) and H3K4me3-anchored chromatin topology (HiChIP) to uncover subtype-independent highly interactive enhancers that interact with essential genes in PDAC. Motif analysis revealed these common enhancers were bound by KLF5 with subsequent depletion leading to decreased cell viability via induction of apoptosis. To elucidate the transcriptional and epigenetic mechanisms by which KLF5 functions in PDAC, we employed rapid depletion of KLF5 with dTAG technology and profiled the effects on the open and active chromatin landscape and transcription with nascent RNA and mRNA-seq over time. Enhancer inactivation via KRAB domain Zim3-dCas9 fusion protein confirmed KLF5-bound enhancers regulate target genes, including the anti-apoptotic gene BCL2L1. Multiplex immunofluorescence confirmed co-staining of KLF5 and Bcl-xL in patient samples and overexpression of Bcl-xL rescued the induction of apoptosis after KLF5 depletion. Taken together, this study provides new insights into common mechanisms to target highly heterogeneous PDAC tumors. TeaserKLF5 controls subtype-independent highly interactive enhancers to regulate cell viability in pancreatic cancer.

cancer biology↗

bioRxiv2025

Epigenetic Context Defines the Transcriptional Activity of Canonical and Noncanonical NF-κB Signaling in Pancreatic Cancer

NF-{kappa}B signaling can be subdivided into canonical and noncanonical pathways, culminating in the transcriptional activity of RELA and RELB, respectively. However, the upstream signals that activate these transcription factors and their specific regulatory roles in pancreatic ductal adenocarcinoma (PDAC) remain incompletely understood. Here, we demonstrate that TNF is the primary activator of canonical NF-{kappa}B signaling via RELA, while TWEAK engages noncanonical signaling through RELB in PDAC. Using transcriptome-wide gene expression, genome-wide occupancy profiling, and epigenome mapping, we delineate distinct temporal dynamics and regulatory activities of each pathway. Single-cell RNA-seq analysis and multiplex immunofluorescence staining in primary PDAC samples further reveal extensive and distinct interactions with components of the tumor microenvironment. Motif analysis of RELA- and RELB-bound regions uncovers a particularly strong association of RELB with AP1 elements. Notably, while RELA binds to both open and closed chromatin, RELB exclusively occupies regions with pre-existing chromatin accessibility and AP1 co-binding. Collectively, these findings underscore the distinct and complementary roles of TNF and TWEAK in PDAC, with TNF engaging a broader transcriptional program via RELA and TWEAK selectively targeting genes marked by accessible chromatin and epigenetic activity. This study provides critical insights into the regulatory dynamics of NF-{kappa}B signaling in PDAC, highlighting unique and complementary functions of RELA and RELB in modulating downstream gene expression. SignificanceTNF and TWEAK selectively activate RELA and RELB in pancreatic cancer, revealing that RELB-driven noncanonical signaling depends on chromatin accessibility and AP-1, uncovering distinct, targetable epigenetic dependencies from canonical signaling. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=59 SRC="FIGDIR/small/661561v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@14aa356org.highwire.dtl.DTLVardef@1297741org.highwire.dtl.DTLVardef@1545741org.highwire.dtl.DTLVardef@2c982b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2018

Pyrite formation from FeS and H2S is mediated by a novel type of microbial energy metabolism

The exergonic reaction of FeS with H2S to form FeS2 (pyrite) and H2 was postulated to have operated as an early form of energy metabolism on primordial Earth. Since the Archean, sedimentary pyrite formation played a major role in the global iron and sulfur cycles, with direct impact on the redox chemistry of the atmosphere. To date, pyrite formation was considered a purely geochemical reaction. Here, we present microbial enrichment cultures, which grew with FeS, H2S, and CO2 as their sole substrates to produce FeS2 and CH4. Cultures grew over periods of three to eight months to cell densities of up to 2-9x106 cells mL-1. Transformation of FeS with H2S to FeS2 was followed by 57Fe Mossbauer spectroscopy and showed a clear biological temperature profile with maximum activity at 28{degrees}C and decreasing activities towards 4{degrees}C and 60{degrees}C. CH4 was formed concomitantly with FeS2 and exhibited the same temperature dependence. Addition of either penicillin or 2-bromoethanesulfonate inhibited both FeS2 and CH4 production, indicating a syntrophic coupling of pyrite formation to methanogenesis. This hypothesis was supported by a 16S rRNA gene-based phylogenetic analysis, which identified at least one archaeal and five bacterial species. The archaeon was closely related to the hydrogenotrophic methanogen Methanospirillum stamsii while the bacteria were most closely related to sulfate-reducing Deltaproteobacteria, as well as uncultured Firmicutes and Actinobacteria. We identified a novel type of microbial metabolism able to conserve energy from FeS transformation to FeS2, which may serve as a model for a postulated primordial iron-sulfur world.\n\nSignificance statementPyrite is the most abundant iron-sulfur mineral in sediments. Over geological times, its burial controlled oxygen levels in the atmosphere and sulfate concentrations in seawater. Its formation in sediments is so far considered a purely geochemical process that is at most indirectly supported by microbial activity. We show that lithotrophic microorganisms can directly transform FeS and H2S to FeS2 and use this exergonic reaction as a novel form of energy metabolism that is syntrophically coupled to methanogenesis. Our results provide insights into a syntrophic relationship that could sustain part of the deep biosphere and lend support to the iron-sulfur-world theory that postulated FeS transformation to FeS2 as a key energy-delivering reaction for life to emerge.

microbiology↗