Active DNA demethylation is critical for controlling the DNA methylomes in plants and mammals. However, little is known about how DNA demethylases are recruited to target loci, and the involvement of chromatin marks in this process. Here, we identify 2 components of the SWR1 chromatin-remodeling complex, PIE1 and ARP6, as required for ROS1-mediated DNA demethylation, and discover 2 SWR1-associated bromodomain-containing proteins, AtMBD9 and nuclear protein X1 (NPX1). AtMBD9 and NPX1 recognize histone acetylation marks established by increased DNA methylation 1 (IDM1), a known regulator of DNA demethylation, redundantly facilitating H2A.Z deposition at IDM1 target loci. We show that at some genomic regions, H2A.Z and DNA methylation marks coexist, and H2A.Z physically interacts with ROS1 to regulate DNA demethylation and antisilencing. Our results unveil a mechanism through which DNA demethylases can be recruited to specific target loci exhibiting particular histone marks, providing a conceptual framework to understand how chromatin marks regulate DNA demethylation.
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http://dx.doi.org/10.1073/pnas.1906023116 | DOI Listing |
Neuron
January 2025
Departments of Psychiatry, Neuroscience, and Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Peter O' Donnell Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:
DNA damage is a major risk factor for the decline of neuronal functions with age and in neurodegenerative diseases. While how DNA damage causes neurodegeneration is still being investigated, innovations over the past decade have provided significant insights into this issue. Breakthroughs in next-generation sequencing methods have begun to reveal the characteristics of neuronal DNA damage hotspots and the causes of DNA damage.
View Article and Find Full Text PDFAnticancer Drugs
January 2025
The First Clinical Medical School, Lanzhou University.
This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profiles of Kasumi-1 and KU812 acute myeloid leukemia cell lines before and after MLN4924 treatment were generated using the 850K Methylation BeadChip. RNA sequencing was used to obtain transcriptomic profiles of Kasumi-1 cells.
View Article and Find Full Text PDFPathogens
December 2024
Department of Botany, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India.
Pathogenic fungi represent a diverse group of eukaryotic microorganisms that significantly impact human health and agriculture. In recent years, the role of epigenetic modifications, particularly histone modifications, in fungal pathobiology has emerged as a prominent area of interest. Among these modifications, methylation of histone H3 at lysine-4 (H3K4) has garnered considerable attention for its implications in regulating gene expression associated with diverse cellular processes.
View Article and Find Full Text PDFMolecules
December 2024
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
DNA methylation and demethylation are key epigenetic events that regulate gene expression and cell fate. DNA demethylation via oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is typically mediated by TET (ten-eleven translocation) enzymes. The 5hmC modification is considered an intermediate state of DNA demethylation; it is particularly prevalent in the brain and is believed to play a role in the development of many cell types in the brain.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Department of Bioinformatics, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators.
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