#redoxepigenetics

Histone H3.1 is a chromatin-embedded redox sensor triggered by tumor cells developing adaptive phenotypic plasticity and multidrug resistance Palma et al. report that H3.1Cys96 oxidation is a functional posttranslational modification involved in the regulation of gene expression. In breast cancer, H3.1Cys96 oxidation promotes resistance to first-line chemotherapeutic drugs and stimulates metastasis. They also show that suppressing H3.1Cys96 oxidation inhibits metastasis while resensitizing cancer cells to chemotherapy.

2024 - the year when we showed that chromatin structure is responsive to ROS regulation because of redox sensitive histone variants - more #redoxepigenetics in 2025 folks - thanks 2024 looking forward to an awesome 2025 www.cell.com/cell-reports...

Temporary HMCES-DNA cross-link prevents permanent DNA damage HMCES, a recently discovered but ancient protein, covalently attaches to damaged single-stranded DNA and shields it from nucleases. Rua-Fernandez and colleagues now show that HMCES catalyzes its own recycling, permitting normal growth and non-mutagenic DNA repair.

Long time not posting about #redoxepigenetics - today the focus is on HMCES a protein that binds to abasic DNA sites caused for instance by guanine oxidation and removed by BER - by protecing those sites HMCES prevents irreparable DNA damage www.cell.com/cell-reports...

An interesting example of #redoxepigenetics in the opposite direction whereby Nupr promoter demethylation drives iron sequestration by lipocalin-2 (lcn2) to reduce iron driven redox dependent cell death

The histone H3-H4 tetramer is a copper reductase enzyme A eukaryotic histone complex can package DNA but is also a cupric reductase that provides biousable Cu1+ for the cell.

H3-H4 histone dimers act as copper reductase. This is important because ETC and SOD1 require bio-usable Cu+ for function. This article shows a new mechanism by which chromatin histones can affect the cell metabolism via a new role in metal processing #redoxepigenetics www.science.org/doi/10.1126/...

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Today the feature is on ROS and R-loops - Hypoxia-driven non-damaging ROS levels lead to R-loop formation. The authors show that ROS-R loop-H3K9Me2 is a key axis regulating chromatin structure and the response to hypoxia. #redoxepigenetics academic.oup.com/nar/article/...

Hierarchical determinants of the oxidation-induced mutational landscape in human cells 8-oxoguanine (8-oxoG) is a common oxidative DNA lesion, which causes G>T substitutions that compose COSMIC single base substitution signature 18 (SBS18) in human cancers. Determinants of local and reg...

This article generated a lot of discussion at #SfRBM2024 and spurred vigorous brain storming sessions - how come 8-oxodG promotes mutations at the most hindered regions of the genome? this is contrary to established paradigm and a phenomenal #redoxepigenetics advance www.biorxiv.org/content/10.1...

Oxidation of HDAC4 by Nox4-derived H2O2 maintains tube formation by endothelial cells NADPH oxidases produce reactive oxygen species that differ in localization, type and concentration. Within the Nox family only Nox4 produces H2O2 whic…

A nice article showing that ROS produced by NADPH oxidase 4 oxidizes class II HDACs epigenetically enforcing endothelial cell lineage identity and tube formation - another great example of #redoxepigenetics suggesting Nox4 works as a nuclear source of ROS? www.sciencedirect.com/science/arti...

Miro1-mediated mitochondrial positioning supports subcellular redox status Mitochondria are strategically trafficked throughout the cell by the action of microtubule motors, the actin cytoskeleton and adapter proteins. The in…

Here the Cunniff lab shows that the positioning of mitochondria relative to the nucleus affects nuclear architecture suggesting mito-generated ROS gradients follow mitos as they reposition actively impacting signaling with superlocal resolution #redoxepigenetics www.sciencedirect.com/science/arti...

Oxidation of Cys 96 only present in heterochromatin associated H3.1 histone promotes its eviction, opens chromatin and facilitates EMT in cancer cells linking metabolically produced ROS and the epigenetic regulation of gene expression #redoxepigenetics www.cell.com/cell-reports...

Developmental ROS individualizes organismal stress resistance and lifespan - Nature A subpopulation of Caenorhabditis elegans, in which there is a naturally occurring transient increase in reactive oxygen species during early development, exhibits increased stress resistance, improve...

Another example of #redoxepigenetics Jakob and colleagues showed that C. elegans exposed to oxidative stress early in life live longer - the authors showed that the oxidation of SET1/COMPASS changes H3K4M3 deposition conferring stress resilience through the lifespan. www.nature.com/articles/s41...

Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications While nitric oxide has been recognized as a key contributor to cancer pathophysiology for many years, this seminal study offers a unifying explanation to help understand why nitric oxide exerts such a...

In this beautiful article authors show that the free radical nitric oxide changes histone PTMs via directly inhibiting iron-dependent Jumonji demethylases - another example of #redoxepigenetics
aacrjournals.org/cancerres/ar...