Biology subjects

Bartke, T.

Publications and source records attributed to Bartke, T..

3 recordsLinked to original sources

bioRxiv2025

Methionine synthase reductase regulates heterochromatin independently of methionine synthesis through mitochondrial homeostasis

Metabolic enzymes can influence chromatin organization by modulating the availability of key metabolites, yet how specific metabolic reactions affect chromatin function remains poorly understood. Here, we show that in Caenorhabditis elegans, the methionine-cycle enzyme methionine synthase reductase (MTRR-l/MSR) regulates heterochromatin independently of methionine synthesis. Loss of MTRR-1, but not of the methionine synthase METR-l/MS, specifically reduces heterochromatic histone methylation, derepresses repetitive elements, and causes developmental delay. Multi-omics profiling revealed that mtrr-1 mutants activate transcriptional programs associated with mitochondrial stress and accumulate long-chain acylcamitines, indicating disrupted mitochondrial homeostasis. Functional assays confirmed altered mitochondrial respiration in mtrr-1 mutants, while genetic suppression of the PMK-3/MAPK mitochondrial retrograde signaling pathway partially restored repeat silencing. Consistently, direct perturbation of mitochondrial function was sufficient to induce heterochromatin derepression in wild type animals. Together, our results reveal a previously unrecognized mitochondria-to-chromatin axis controlled by the methionine-cycle enzyme MTRR-l/MSR, demonstrating that mitochondrial homeostasis is required for heterochromatin maintenance independently of canonical methionine metabolism.

cell biology↗

bioRxiv2024

asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers

Chromatin, the nucleoprotein complex consisting of DNA and histone proteins, plays a crucial role in regulating gene expression by controlling access to DNA. Chromatin modifications are key players in this regulation, as they help to orchestrate DNA transcription, replication, and repair. These modifications recruit epigenetic "reader" proteins, which mediate downstream events. Most modifications occur in distinctive combinations within a nucleosome, suggesting that epigenetic information can be encoded in combinatorial chromatin modifications. A detailed understanding of how multiple modifications cooperate in recruiting such proteins has, however, remained largely elusive. Here, we integrate nucleosome affinity purification data with high-throughput quantitative proteomics and hierarchical interaction modeling to estimate combinatorial effects of chromatin modifications on protein recruitment. This is facilitated by the computational workflow asteRIa which combines hierarchical interaction modeling, stability-based model selection, and replicate-consistency checks for a stable estimation of Robust Interactions among chromatin modifications. asteRIa identifies several epigenetic reader candidates responding to specific interactions between chromatin modifications. For the polycomb protein CBX8, we independently validate our results using genome-wide ChIP-Seq and bisulphite datasets. We provide the first quantitative framework for identifying cooperative effects of chromatin modifications on protein binding.

molecular biology↗

bioRxiv2020

Live-cell 3D single-molecule tracking reveals how NuRD modulates enhancer dynamics

Enhancer-promoter dynamics are crucial for the spatiotemporal control of gene expression, but it remains unclear whether these dynamics are controlled by chromatin regulators, such as the nucleosome remodelling and deacetylase (NuRD) complex. The NuRD complex binds to all active enhancers to modulate transcription and here we use Hi-C experiments to show that it blurs TAD boundaries and increases the proximity of intermediate-range (~1 Mb) genomic sequences and enhancer-promoter interactions. To understand whether NuRD alters the dynamics of 3D genome structure, we developed an approach to segment and extract key biophysical parameters from 3D single-molecule trajectories of the NuRD complex determined using live-cell imaging. Unexpectedly, this revealed that the intact NuRD complex decompacts chromatin structure and makes NuRD-bound enhancers move faster, increasing the overall volume of the nucleus that these key regulatory regions explore. Interestingly, we also uncovered a rare fast-diffusing state of NuRD bound enhancers that exhibits directed motion. The NuRD complex reduces the amount of time that enhancers remain in this fast-diffusing state, which we propose might otherwise re-organise enhancer-promoter proximity. Thus, we uncover an intimate connection between a chromatin remodeller and the spatial dynamics of the local regions of the genome to which it binds.

cell biology↗