Back

The KRAB-Zinc Finger protein ZKSCAN3 represses enhancers via embedded retrotransposons

Moore, D.; Wong, E.; Arnal, C.; Schoenfelder, S. W.; Spivakov, M.; Andrews, S.; Christophorou, M. A.

2025-01-31 molecular biology
10.1101/2025.01.30.635440 bioRxiv
Show abstract

Gene cis-regulatory sequences are increasingly recognised as containing "domesticated" transposable elements that impact their function. The KRAB Zinc Finger Protein (KZFP) family of transcription factors is typically associated with transposable element silencing through establishment of heterochromatin. Here, using acute protein depletion in embryonic stem cells, we reveal that the KZFP ZKSCAN3 represses enhancer activity through targeting enhancer-embedded retrotransposons and that ZKSCAN3-mediated repression does not rely on the induction of heterochromatin. ZKSCAN3, which exhibits strong genetic association with the neurodevelopmental disorder schizophrenia, operates during neural differentiation and is necessary for proper cell specification and expression of genes that regulate axon guidance, neuronal motility and pathfinding. These findings define ZKSCAN3 as an enhancer regulator and uncover a heterochromatin-independent KZFP. Additionally, they exemplify how a KZFP epigenetically regulates enhancers in a native setting and highlight how transposable elements and their KZFP binders have shaped gene expression networks.

Matching journals

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

1
Nature Communications
○ 5641 papers in training set
Top 4%
26.5%
Similar papers in this journal
2
Molecular Cell
○ 350 papers in training set
Top 0.3%
12.7%
Similar papers in this journal
3
Cell Genomics
○ 172 papers in training set
Top 0.5%
6.7%
Similar papers in this journal
4
Cell Reports
○ 1498 papers in training set
Top 4%
6.7%
Similar papers in this journal
50% of probability mass above
5
Nature Structural & Molecular Biology
236 papers in training set
Top 0.9%
4.8%
6
Science Advances
● 1243 papers in training set
Top 6%
4.8%
7
Nucleic Acids Research
◐ 1281 papers in training set
Top 5%
3.2%
8
eLife
● 5828 papers in training set
Top 35%
3.2%
9
Nature Genetics
○ 286 papers in training set
Top 2%
3.2%
10
Genome Biology
○ 637 papers in training set
Top 4%
3.2%
11
Cell
○ 431 papers in training set
Top 4%
2.4%
12
Communications Biology
○ 993 papers in training set
Top 9%
2.4%
13
Genes & Development
● 90 papers in training set
Top 0.6%
2.1%
14
Nature Cell Biology
○ 118 papers in training set
Top 2%
1.7%
15
The EMBO Journal
○ 309 papers in training set
Top 3%
1.7%
16
Nature
○ 645 papers in training set
Top 7%
1.5%
17
Genome Research
● 468 papers in training set
Top 4%
1.4%
18
iScience
○ 1154 papers in training set
Top 30%
1.0%
19
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 38%
1.0%
20
EMBO Reports
○ 263 papers in training set
Top 8%
0.6%
21
PLOS Biology
● 486 papers in training set
Top 13%
0.6%
22
Science
● 477 papers in training set
Top 10%
0.6%
23
Scientific Reports
○ 3612 papers in training set
Top 77%
0.6%

"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.