Back

Multiple redundant mechanisms account for the majority of gene silencing downstream of DNA methylation

Wang, S.; Wu, Z.; Li, Z.; Movilli, A.; He, L.; Zhou, Y.; Lin, E. K.; Chuang, R.; Thiri, W. W.; Convery, S.; Feng, S.; Weigel, D.; Jacobsen, S. E.

2026-02-10 molecular biology
10.64898/2026.02.08.704674 bioRxiv
Show abstract

DNA methylation is a conserved epigenetic modification crucial for silencing genes and transposable elements (TEs). However, the mechanisms that cause silencing remain unclear, partly because methyl reader protein mutants in both plants and animals show minimal transcriptional changes. To explore the possibility of redundancy among these silencing mechanisms, we generated combinatorial mutants of H1.1, H1.2, ADCP1, MOM1, MBD2, MBD5, and MBD6 lacking key methyl readers and related silencing pathways. We observed massive derepression of genes and TEs at DNA-methylated loci, showing that these pathways account for 73% of silencing compared to DNA methylation-free mutants. We also observed that immune response genes were upregulated, causing an imbalance between growth and defense. Loss of downstream silencing pathways further disrupted 3D genome organization, leading to increased euchromatin-heterochromatin interactions. These findings highlight the cooperative action of multiple downstream mechanisms in DNA methylation-mediated silencing and genome organization.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
Genome Biology
○ 637 papers in training set
Top 0.2%
22.3%
Similar papers in this journal
2
Epigenetics & Chromatin
52 papers in training set
Top 0.1%
13.2%
3
PLOS Genetics
● 862 papers in training set
Top 0.8%
11.2%
Similar papers in this journal
4
Nature Communications
○ 5641 papers in training set
Top 22%
7.4%
Similar papers in this journal
50% of probability mass above
5
Mobile DNA
○ 31 papers in training set
Top 0.1%
5.6%
Similar papers in this journal
6
Nucleic Acids Research
◐ 1281 papers in training set
Top 4%
5.2%
7
Genome Research
● 468 papers in training set
Top 2%
3.6%
8
Cell Reports
○ 1498 papers in training set
Top 12%
3.2%
9
eLife
● 5828 papers in training set
Top 38%
2.8%
10
Advanced Science
○ 286 papers in training set
Top 3%
2.2%
11
Science Advances
● 1243 papers in training set
Top 19%
1.8%
12
Nature Structural & Molecular Biology
236 papers in training set
Top 2%
1.7%
13
PLOS Biology
● 486 papers in training set
Top 5%
1.5%
14
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 30%
1.5%
15
Molecular Cell
○ 350 papers in training set
Top 4%
1.1%
16
iScience
○ 1154 papers in training set
Top 25%
1.1%
17
BMC Biology
○ 265 papers in training set
Top 3%
1.1%
18
Communications Biology
○ 993 papers in training set
Top 20%
1.1%
19
PLOS ONE
● 5266 papers in training set
Top 58%
0.9%
20
Cell Genomics
○ 172 papers in training set
Top 4%
0.9%
21
Scientific Reports
○ 3612 papers in training set
Top 71%
0.9%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.