ADNP regulates chromatin architecture and lineage fidelity during neural differentiation.
Overview
- Gene expression and Regulation program, The Wistar Institute, Philadelphia, Pennsylvania, United States of America
- Epigenetics Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
- Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Abstract
Transition from a pluripotent to a differentiated cell state is accompanied by significant changes in genome organization. Activity dependent neuroprotective protein (ADNP) is a chromatin regulator with critical roles in neurodevelopment and limits the genomic occupancy of CTCF, a master architectural protein in genome organization, in embryonic stem cells. However, ADNP localization, function, and relationship with CTCF in differentiated neural lineages are not well studied. Here we develop a dual degron model which allows us to acutely deplete ADNP in neural progenitor cells (NPCs). We find that ADNP depletion does not impact NPC survival in the short term, but results in a genome organization switch, which favors the formation of short-range chromatin looping interactions coinciding with CTCF accumulation. Furthermore, ADNP localizes to active gene promoters in NPCs that are unoccupied by CTCF, where it prevents over-expression of genes that are activated upon neurodifferentiation and represses those involved in commitment to other lineages. Our findings uncover CTCF-dependent as well as CTCF-independent regulatory mechanisms of ADNP in NPC-specific chromatin organization and gene expression programs that may underlie its essential function in neurodevelopment.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper links to its data, not to its authors' code: see the Data section.
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Data
Datasets cited
- geo:GSE252218, at NCBI GEO; found in the text, “External data.”
Data Availability
Sequencing data have been deposited at GEO and are publicly available as of the date of publication under accession number GSE303981. All other relevant data are in the manuscript and its supporting information files.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 15 MeSH terms, 6 funders, 67 references.
Cite
This paper
Wulfridge, P., Rell, N., Doherty, J., Fang, K.-C., Lynskey, M. L., & Sarma, K. (2026). ADNP regulates chromatin architecture and lineage fidelity during neural differentiation. PLoS genetics, 22(4), e1012081. https://
BibTeX
@article{wulfridge2026ad
author = {Wulfridge, Phillip and Rell, Nathaniel and Doherty, John and Fang, Kuo-Chen and Lynskey, Michelle Lee and Sarma, Kavitha},
title = {{ADNP regulates chromatin architecture and lineage fidelity during neural differentiation}},
journal = {PLoS genetics},
year = {2026},
month = apr,
volume = {22},
number = {4},
pages = {e1012081},
publisher = {PLOS},
issn = {1553-7390},
doi = {10.1371/
url = {https://
pmid = {41920822},
pmcid = {PMC13061322}
}
RIS
TY - JOUR
AU - Wulfridge, Phillip
AU - Rell, Nathaniel
AU - Doherty, John
AU - Fang, Kuo-Chen
AU - Lynskey, Michelle Lee
AU - Sarma, Kavitha
TI - ADNP regulates chromatin architecture and lineage fidelity during neural differentiation
T2 - PLoS genetics
J2 - PLoS Genet
PY - 2026
DA - 2026/
VL - 22
IS - 4
SP - e1012081
SN - 1553-7390
PB - PLOS
DO - 10.1371/
UR - https://
LA - en
ER -
CSL-JSON
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