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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

From chromatin to crop: epigenetic innovations in bioenergy systems

Energy crops encompass a diverse array of plant species cultivated primarily as a source of biomass for energy generation and biofuel production. As such, they play a pivotal role in the transition to sustainable energy systems. However, their productivity is often limited by environmental stresses, nutrient availability, and the need for optimized yield. While traditional breeding and genetic engineering have driven improvements, challenges such as narrow genetic diversity, long development cycles, trait instability, and unexpected gene interactions remain. Epigenetics offers a largely untapped opportunity to overcome these constraints by regulating gene expression through mechanisms that are dynamic, finely tuned, and responsive to environmental and developmental cues. Epigenetic modifications including DNA methylation, histone post-translational changes, and small non-coding RNAs influence nearly all aspects of plant development and physiology, including traits central to bioenergy crops. While these mechanisms are well characterized in model species such as Arabidopsis thaliana, they remain underexplored in many purpose-grown energy crops. This review summarizes the current state of knowledge of epigenetic regulation in bioenergy species, explores how these mechanisms can be leveraged to enhance crop resilience and productivity, and identifies gaps in our understanding. By characterizing epigenetic mechanisms and harnessing epigenetic variation, we can expand the toolkit for developing resilient, high-yielding bioenergy crops to meet future environmental and energy demands.

09 BIOMASS FUELS↗
NASA NTRS2002

Induction of chromatin damage and distribution of isochromatid breaks in human fibroblast cells exposed to heavy ions

The frequency of chromatid breaks and the distribution of isochromatid breaks were measured in G2-phase normal human fibroblasts prematurely condensed a short time after exposure to low- or high-LET radiations. The average number of isochromatid breaks from a single particle traversal increased with increasing LET values, while the average number of chromatid-type breaks appeared to reach a plateau. The distribution of isochromatid breaks after high-LET iron particles exposure was overdispersed compared to gamma-rays, indicating that a single iron particle traversal through a cell nucleus can produce multiple isochromatid breaks.

NASA Center JSC↗
NASA NTRS1998

Rejoining and misrejoining of radiation-induced chromatin breaks. III. Hypertonic treatment

It has been shown that treatment in anisotonic medium modifies rejoining of radiation-induced breaks in interphase chromosomes. In previous work, we have demonstrated that formation of exchanges in human lymphocytes has a slow component (half-time of 1-2 h), but a fraction of exchanges are also observed in samples assayed soon after exposure. In this paper we studied the effect of hypertonic treatment on rejoining and misrejoining of radiation-induced breaks using fluorescence in situ hybridization of prematurely condensed chromosomes in human lymphocytes. Isolated lymphocytes were irradiated with 7 Gy gamma rays, fused to mitotic hamster cells and incubated in hypertonic solution (0.5 M NaCl) for the period normally allowed for interphase chromosome condensation to occur. The data from hypertonic treatment experiments indicate the presence of a class of interphase chromosome breaks that rejoin and misrejoin very quickly (half-time of 5-6 min). The fast misrejoining of these lesions is considered to be responsible for the initial level of exchanges which we reported previously. No significant effect of hypertonic treatment on the yield of chromosome aberrations scored at the first postirradiation mitosis was detected.

NASA Discipline Radiation Health↗
NASA NTRS1996

Rejoining and misrejoining of radiation-induced chromatin breaks. II. Biophysical Model

A biophysical model for the kinetics of the formation of radiation-induced chromosome aberrations is developed to account for the recent experimental results obtained with a combination of the premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) techniques. In this model, we consider the broken ends of DNA double-strand breaks (DSBs) to be reactant and make use of the interaction distance hypothesis. The repair/misrepair process between broken ends is suggested to consist of two steps; the first step represents the two break ends approaching each other, and the second step represents the enzymatic processes leading to DNA end-to-end rejoining. Only the second step is reflected in the kinetics observed in experiments using PCC. The model appears to be able to fit existing data for human cells. It is shown that the kinetics of the formation of chromosome aberrations can be explained by a single rate that characterizes both rejoining and misrejoining of DSBs, suggesting that repair and misrepair share the same mechanism. Fast repair (completed in minutes) in a subset of DSBs is suggested as an explanation of the complete exchanges observed with PCC in human lymphocytes immediately after irradiation. The fast repair component seems to be absent in human fibroblasts.

NASA Center JSC↗
NASA NTRS1996

Rejoining and misrejoining of radiation-induced chromatin breaks. I. experiments with human lymphocytes

Fluorescence in situ hybridization with a composite probe for human chromosome 4 and a probe that stained all centromeres was used to study gamma-ray induced breakage, rejoining and misrejoining in prematurely condensed chromosomes in human lymphocytes. Dose-response curves for the induction of all types of aberrations in prematurely condensed human chromosomes 4 were determined immediately after irradiation and after 8 h postirradiation incubation. In addition, aberrations were measured after various incubation times from 0 to 18 h after a dose of 7 Gy. Unrejoined chromosome breaks were the most frequent type of aberration observed immediately after irradiation. Approximately 15% of total aberrations observed were chromosome exchanges. After 8 h postirradiation incubation, the frequency of breaks in prematurely condensed chromosomes declined to about 20% of the initial value, and chromosomal exchanges became the most frequent aberration. Results of metaphase analysis were similar to those for prematurely condensed chromosomes after 8 h incubation with the exception that a significantly lower frequency of fragments was observed. Symmetrical and asymmetrical interchanges were found at similar frequencies at all doses. No complex exchanges were observed in lymphocyte chromosomes immediately after exposure. They accounted for about 1% of total exchanges in metaphase chromosomes at doses <3 Gy and about 14% at 7 Gy. Incomplete exchanges amounted to approximately 15% of total exchanges at all doses. The kinetics of break rejoining was exponential, and the frequency of exchanges increased with kinetics similar to that observed for the rejoining of the breaks. This increase in the total exchanges as a function of the time between irradiation and fusion was due to a rapid increase in reciprocal interchanges, and a slower increase in complex exchanges; the frequency of incomplete exchanges increased initially, then decreased with prolonged incubation to the level observed in metaphase. It is concluded that the formation of each kind of chromosome aberrations follows different kinetics.

NASA Discipline Radiation Health↗
DOE OSTI2020

Chromatin activity precipitation method and system

Methods and systems for identifying binding sites in macromolecules using small molecule mimics of naturally occurring molecules is disclosed. A reactive probe is provided that mimics small molecule cofactors. A target macromolecule is irreversibly bound to the probe in vivo to selectively pull down or precipitate probe-bound macromolecules. The macromolecules may be, but are not limited to, DNA, RNA, and proteins.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Physical models reveal indirect reader protein interactions that facilitate epigenetic crosstalk

The spatial organization of chromatin is governed by epigenetic factors, including epigenetic marks and the reader proteins that bind them. By dictating the accessibility of genomic loci, epigenetic factors contribute to the physical regulation of gene expression, enabling diverse cellular phenotypes to be encoded by a shared genome in an individual. Epigenetic dysregulation can lead to aberrations in chromatin architecture, contributing to diseases such as neurological disorders and cancers. Despite the known importance of chromatin organization for human health, the physical mechanisms governing chromatin folding remain underspecified. In this work, we develop a physical model of chromatin organization based on contributions from multiple epigenetic factors. Using our model, we evaluate how conditions in the nuclear environment and crosstalk between epigenetic marks affect the compartmentalization of chromatin into dense heterochromatin and loose euchromatin. Our results emphasize the role of reader protein binding in chromatin compartmentalization. We show that reader proteins interact through an indirect mechanism facilitated by the shared chromatin “scaffold” to which they bind. Under a scenario where reader proteins compete for binding sites, we find that indirect interactions affect the program adopted by the chromatin fiber. By isolating indirect modes of epigenetic crosstalk, we demonstrate how the interplay between epigenetic patterning and environmental factors influences chromatin architecture.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Uncovering hidden enhancers through unbiased in vivo testing

Chromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental enhancers with tissue-matched chromatin data, 14% (n = 285) lacked canonical enhancer-associated chromatin signatures. To further assess the prevalence of enhancers missed by chromatin profiling approaches, we used a high-throughput transgenic enhancer assay to screen the regulatory landscapes of two key developmental genes at 5 kb resolution, spanning 1.3 Mb of mouse sequence in total. We observed that 23 of 88 (26%) in vivo enhancers discovered by this approach lacked enhancer-associated chromatin signatures in the respective tissue. Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.

Epigenomics↗
DOE OSTI2022

The histone code of the fungal genus Aspergillus uncovered by evolutionary and proteomic analyses

Chemical modifications of DNA and histone proteins impact the organization of chromatin within the nucleus. Changes in these modifications, catalysed by different chromatin-modifying enzymes, influence chromatin organization, which in turn is thought to impact the spatial and temporal regulation of gene expression. While combinations of different histone modifications, the histone code, have been studied in several model species, we know very little about histone modifications in the fungal genus Aspergillus, whose members are generally well studied due to their importance as models in cell and molecular biology as well as their medical and biotechnological relevance. Here, we used phylogenetic analyses in 94 Aspergilli as well as other fungi to uncover the occurrence and evolutionary trajectories of enzymes and protein complexes with roles in chromatin modifications or regulation. We found that these enzymes and complexes are highly conserved in Aspergilli, pointing towards a complex repertoire of chromatin modifications. Nevertheless, we also observed few recent gene duplications or losses, highlighting Aspergillus species to further study the roles of specific chromatin modifications. SET7 (KMT6) and other components of PRC2 (Polycomb Repressive Complex 2), which is responsible for methylation on histone H3 at lysine 27 in many eukaryotes including fungi, are absent in Aspergilli as well as in closely related Penicillium species, suggesting that these lost the capacity for this histone modification. We corroborated our computational predictions by performing untargeted MS analysis of histone post-translational modifications in Aspergillus nidulans. This systematic analysis will pave the way for future research into the complexity of the histone code and its functional implications on genome architecture and gene regulation in fungi.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues

While a rich set of putative cis-regulatory sequences involved in mouse fetal development have been annotated recently on the basis of chromatin accessibility and histone modification patterns, delineating their role in developmentally regulated gene expression continues to be challenging. To fill this gap, here we mapped chromatin contacts between gene promoters and distal sequences across the genome in seven mouse fetal tissues and across six developmental stages of the forebrain. We identified 248,620 long-range chromatin interactions centered at 14,138 protein-coding genes and characterized their tissue-to-tissue variations and developmental dynamics. Integrative analysis of the interactome with previous epigenome and transcriptome datasets from the same tissues revealed a strong correlation between the chromatin contacts and chromatin state at distal enhancers, as well as gene expression patterns at predicted target genes. We predicted target genes of 15,098 candidate enhancers and used them to annotate target genes of homologous candidate enhancers in the human genome that harbor risk variants of human diseases. We present evidence that schizophrenia and other adult disease risk variants are frequently found in fetal enhancers, providing support for the hypothesis of fetal origins of adult diseases.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Structure and functional determinants of Rad6–Bre1 subunits in the histone H2B ubiquitin-conjugating complex

The conserved complex of the Rad6 E2 ubiquitin-conjugating enzyme and the Bre1 E3 ubiquitin ligase catalyzes histone H2B monoubiquitination (H2Bub1), which regulates chromatin dynamics during transcription and other nuclear processes. Here, we report a crystal structure of Rad6 and the non-RING domain N-terminal region of Bre1, which shows an asymmetric homodimer of Bre1 contacting a conserved loop on the Rad6 ‘backside’. This contact is distant from the Rad6 catalytic site and is the location of mutations that impair telomeric silencing in yeast. Mutational analyses validated the importance of this contact for the Rad6–Bre1 interaction, chromatin-binding dynamics, H2Bub1 formation and gene expression. Moreover, the non-RING N-terminal region of Bre1 is sufficient to confer nucleosome binding ability to Rad6 in vitro. Interestingly, Rad6 P43L protein, an interaction interface mutant and equivalent to a cancer mutation in the human homolog, bound Bre1 5-fold more tightly than native Rad6 in vitro, but showed reduced chromatin association of Bre1 and reduced levels of H2Bub1 in vivo. These surprising observations imply conformational transitions of the Rad6–Bre1 complex during its chromatin-associated functional cycle, and reveal the differential effects of specific disease-relevant mutations on the chromatin-bound and unbound states. Overall, our study provides structural insights into Rad6–Bre1 interaction through a novel interface that is important for their biochemical and biological responses.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1996

Clusters of DNA induced by ionizing radiation: formation of short DNA fragments. I. Theoretical modeling

We have developed a general theoretical model for the interaction of ionizing radiation with chromatin. Chromatin is modeled as a 30-nm-diameter solenoidal fiber comprised of 20 turns of nucleosomes, 6 nucleosomes per turn. Charged-particle tracks are modeled by partitioning the energy deposition between primary track core, resulting from glancing collisions with 100 eV or less per event, and delta rays due to knock-on collisions involving energy transfers >100 eV. A Monte Carlo simulation incorporates damages due to the following molecular mechanisms: (1) ionization of water molecules leading to the formation of OH, H, eaq, etc.; (2) OH attack on sugar molecules leading to strand breaks: (3) OH attack on bases; (4) direct ionization of the sugar molecules leading to strand breaks; (5) direct ionization of the bases. Our calculations predict significant clustering of damage both locally, over regions up to 40 bp and over regions extending to several kilobase pairs. A characteristic feature of the regional damage predicted by our model is the production of short fragments of DNA associated with multiple nearby strand breaks. The shapes of the spectra of DNA fragment lengths depend on the symmetries or approximate symmetries of the chromatin structure. Such fragments have subsequently been detected experimentally and are reported in an accompanying paper (B. Rydberg, Radiat, Res. 145, 200-209, 1996) after exposure to both high- and low-LET radiation. The overall measured yields agree well quantitatively with the theoretical predictions. Our theoretical results predict the existence of a strong peak at about 85 bp, which represents the revolution period about the nucleosome. Other peaks at multiples of about 1,000 bp correspond to the periodicity of the particular solenoid model of chromatin used in these calculations. Theoretical results in combination with experimental data on fragmentation spectra may help determine the consensus or average structure of the chromatin fibers in mammalian DNA.

Non-NASA Center↗
NASA NTRSDate not supplied

Simulation of Radiation-Induced DNA Damage With the Code RITRACKS

INTRODUCTION DNA damage is one of the most physiologically important effects of ionizing radiation. Clustered DNA damage events, like double-strand breaks (DSBs), have the most notable biological consequences. DNA damage types depend on both the track structure of the radiation and the spatial organization of the DNA. High linear energy transfer (LET) charged nuclei, found in galactic cosmic rays (GCR), are known to produce large numbers of complex DNA damage events. The human genome is packaged into chromatin, which can take on locus-dependent and cell type-dependent spatial conformations that correspond to epigenetic states, such as more open, extended structures in transcriptionally active chromatin. These epigenetic differences can affect DNA break patterns in response to ionizing radiation, potentially creating distinct DNA repair and signaling outcomes across the genome in different cells. MATERIAL AND METHODS The code RITRACKS (Relativistic Ion Tracks), which simulates stochastic radiation track structures and radiation chemistry, was used to model damage on isolated and histone-bound DNA by various types of ions and photons. The changes made to the code to perform radiation-induced DNA damage, and simulation results on single nucleosomes are given in our recent paper. In this work, the DNA building capabilities of RITRACKS have been extended to simulate more complex DNA structures build on the coarse-grain simulation framework meso-WLCsim. This code can sample generic chromatin fiber conformation ensembles based on the geometry of nucleosomes and mechanical properties of DNA. Using RITRACKS, we simulated the fragment length distributions (FLD) of irradiated DNA structures built using the chromatin conformations of WLCsim and obtained results representative of those obtained with Radiation-Induced Correlated Cleavage with sequencing (RICC-Seq) experiments [6]. We have also performed Fe ion and photon irradiations of K562, IMR90, BJ and RPE-1 cells at NSRL to experimentally validate results. Sample processing and data analysis are in progress and any available preliminary results will be discussed. DISCUSSION The recent updates in the code RITRACKS allow the calculation of several quantities such as the DNA damage yield and the FLD. This approach can be used to model epigenetic state-specific chromatin structure parameters to leverage the epigenetic state data available for many human cell types to infer relative DNA damage sensitivity among genomic loci.

I Plante↗