Evidence map›Paper›PMID 42465491›Full record

ArticlebioRxiv : the preprint server for biology2026

Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.

Jinna I Brim, Izaiah J Ornelas, Peter J Colias, Nikita S Divekar, Da Xu, Justin P Lubin, Sophia I Ferrel, Luis Galán Palma, Mitzi G Hernández Zamora, Rithu K Pattali and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Jinna I BrimDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Izaiah J OrnelasDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Peter J ColiasDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Nikita S DivekarDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Da XuDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Justin P LubinDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
Sophia I FerrelDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Luis Galán PalmaDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Mitzi G Hernández ZamoraDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Rithu K PattaliDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Jameel J McDanielDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Sarah E ChasinsDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA, USA.
James K NuñezDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.ORCID 0000-0002-7396-6119

Funding

Genetic Dissection of Cells and Organisms Training ProgramT32GM132022 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Nicole King, NOAH K WHITEMAN · 2019 to 2026
$5.2M
Mechanisms of epigenetic memory in human cellsR35GM155044 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI James Karlo Nunez · 2024 to 2026
$1.2M
Illumina NovaSeq 6000 Sequencing SystemS10OD028511 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHOW, ERIC D · 2020 to 2020
$583k
NIGMS NIH HHS R35 GM155044NIGMS NIH HHS T32 GM132022NIH HHS S10 OD028511
6 · The paper itself

Abstract

The ability to control the expression of human genes is a major goal in synthetic biology, enables dissection of gene function, and can be harnessed for therapeutic applications. Advances in genome editing and transcriptional engineering often result in complete gene inactivation or full transcriptional repression. However, programmable tools to dial transcription at intermediate levels remain challenging. Here, we present CRISPRtune - a synthetic fusion of MeCP2 to catalytically dead dCas9 that tunes down transcription of endogenous genes in human cells by harnessing the mild repressor activity of MeCP2. Using pooled genome-scale CRISPR screens, we tune the expression of thousands of endogenous genes and define the targeting rules of CRISPRtune in human cells. With a platform to target MeCP2 at defined genomic sites, we show the direct epigenetic changes induced by MeCP2 at gene promoters and we identify its genetic dependency partners for productive transcriptional repression. Rett syndrome-associated mutations of MeCP2 show defects for transcriptional repression due to their failure to remodel the local epigenetic landscape of target genes. Together, we present a programmable method for transcriptional tuning in mammalian cells and offer an orthogonal platform to dissect the mechanistic function of chromatin regulators in living cells.

Identifiers

PMID42465491
PMCPMC13370360

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.