Jesse Engreitz
@jengreitz.bsky.social
Assistant Professor @ Stanford Genetics & BASE Initiative. Mapping the regulatory code of the human genome to understand heart development and disease. www.engreitzlab.org
These unbiased CRISPRi datasets will help to evaluate predictive models (stay tuned for results for scE2G and ENCODE-rE2G)
Here, we show that this evaluation must account for the magnitude of effect sizes, frequency of indirect effects, chromatin states, and gene class.
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Here, we show that this evaluation must account for the magnitude of effect sizes, frequency of indirect effects, chromatin states, and gene class.
11/
September 19, 2025 at 3:03 AM
These unbiased CRISPRi datasets will help to evaluate predictive models (stay tuned for results for scE2G and ENCODE-rE2G)
Here, we show that this evaluation must account for the magnitude of effect sizes, frequency of indirect effects, chromatin states, and gene class.
11/
Here, we show that this evaluation must account for the magnitude of effect sizes, frequency of indirect effects, chromatin states, and gene class.
11/
17% of regulatory elements corresponding to sites that bind CTCF only (no/very low H3K27ac).
The large frequency of these sites (likely, CTCF binding sites that may regulate 3D contacts) has been missed in some previous studies due to selecting elements with high H3K27ac.
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The large frequency of these sites (likely, CTCF binding sites that may regulate 3D contacts) has been missed in some previous studies due to selecting elements with high H3K27ac.
9/
September 19, 2025 at 3:03 AM
17% of regulatory elements corresponding to sites that bind CTCF only (no/very low H3K27ac).
The large frequency of these sites (likely, CTCF binding sites that may regulate 3D contacts) has been missed in some previous studies due to selecting elements with high H3K27ac.
9/
The large frequency of these sites (likely, CTCF binding sites that may regulate 3D contacts) has been missed in some previous studies due to selecting elements with high H3K27ac.
9/
Nearly half of significant effects were likely to be indirect
– including nearly all of the examples of ‘up-regulation’.
So, CRISPRi is not, for example, finding lots of silencing elements.
8/
– including nearly all of the examples of ‘up-regulation’.
So, CRISPRi is not, for example, finding lots of silencing elements.
8/
September 19, 2025 at 3:03 AM
Nearly half of significant effects were likely to be indirect
– including nearly all of the examples of ‘up-regulation’.
So, CRISPRi is not, for example, finding lots of silencing elements.
8/
– including nearly all of the examples of ‘up-regulation’.
So, CRISPRi is not, for example, finding lots of silencing elements.
8/
Most effect sizes were in the range of 5-10% — much smaller than effect sizes observed in previous studies.
This was not due to technical differences but rather differences in statistical power and element/gene selection bias.
7/
This was not due to technical differences but rather differences in statistical power and element/gene selection bias.
7/
September 19, 2025 at 3:03 AM
Most effect sizes were in the range of 5-10% — much smaller than effect sizes observed in previous studies.
This was not due to technical differences but rather differences in statistical power and element/gene selection bias.
7/
This was not due to technical differences but rather differences in statistical power and element/gene selection bias.
7/
Background: We and others have previously used CRISPRi to perturb thousands of candidate regulatory elements and measure their effects on expression.
These studies have yielded insights about regulatory element function and enabled us to build predictive models like ABC and ENCODE-rE2G
2/
These studies have yielded insights about regulatory element function and enabled us to build predictive models like ABC and ENCODE-rE2G
2/
September 19, 2025 at 3:03 AM
Background: We and others have previously used CRISPRi to perturb thousands of candidate regulatory elements and measure their effects on expression.
These studies have yielded insights about regulatory element function and enabled us to build predictive models like ABC and ENCODE-rE2G
2/
These studies have yielded insights about regulatory element function and enabled us to build predictive models like ABC and ENCODE-rE2G
2/
New preprint from our lab!
What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?
Find out here: www.biorxiv.org/content/10.1...
👇
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What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?
Find out here: www.biorxiv.org/content/10.1...
👇
1/
September 19, 2025 at 3:03 AM
New preprint from our lab!
What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?
Find out here: www.biorxiv.org/content/10.1...
👇
1/
What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?
Find out here: www.biorxiv.org/content/10.1...
👇
1/
September 18, 2025 at 4:14 PM
… and see which variants in LD with your query also overlap enhancers:
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September 18, 2025 at 4:14 PM
… and see which variants in LD with your query also overlap enhancers:
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1. Search for your favorite GWAS variant and find predicted target genes and cell types (e.g. e2g.stanford.edu/variant/10_7...):
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September 18, 2025 at 4:14 PM
1. Search for your favorite GWAS variant and find predicted target genes and cell types (e.g. e2g.stanford.edu/variant/10_7...):
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Our latest work now online in Cell:
Rewriting regulatory DNA to dissect and reprogram gene expression
Our new method (Variant-EFFECTS) uses high-throughput prime editing + flow sorting + sequencing to precisely measure effects of noncoding variants on gene expression
Thread 👇
Rewriting regulatory DNA to dissect and reprogram gene expression
Our new method (Variant-EFFECTS) uses high-throughput prime editing + flow sorting + sequencing to precisely measure effects of noncoding variants on gene expression
Thread 👇
April 17, 2025 at 6:26 PM
Our latest work now online in Cell:
Rewriting regulatory DNA to dissect and reprogram gene expression
Our new method (Variant-EFFECTS) uses high-throughput prime editing + flow sorting + sequencing to precisely measure effects of noncoding variants on gene expression
Thread 👇
Rewriting regulatory DNA to dissect and reprogram gene expression
Our new method (Variant-EFFECTS) uses high-throughput prime editing + flow sorting + sequencing to precisely measure effects of noncoding variants on gene expression
Thread 👇