---
title: "BAF complex cooperates with FOS to control activity-dependent ASD-linked gene programs in human ne"
id: "biorxiv-13-the-baf-complex-works-with-fos-to-regulate-human-neuronal-activity-dependent"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-13-the-baf-complex-works-with-fos-to-regulate-human-neuronal-activity-dependent"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.25.747063v1?rss=1"
published_at: "2026-08-27T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# BAF complex cooperates with FOS to control activity-dependent ASD-linked gene programs in human ne
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-13-the-baf-complex-works-with-fos-to-regulate-human-neuronal-activity-dependent
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.25.747063v1?rss=1)
- **Published At:** 2026-08-27T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study investigates how the **BAF chromatin remodeling complex** is directed across the human neuronal genome and how it regulates activity-dependent gene programs linked to autism spectrum disorder (**ASD**). - Authors report that BAF co-binds with the activity-dependent transcription factor **FOS** at distal regulatory regions that open chromatin and exhibit enhancer activation in response to neuronal activity. - Knock-out of ARID1A, a BAF subunit implicated in ASD, reduces chromatin accessibility at regions bound by FOS and BAF and lowers expression of nearby activity-regulated, ASD-associated genes. - The FOS binding motif within regions co-bound by FOS and BAF is highly constrained in the human population, suggesting functional importance. - Rare variants in this FOS motif, identified in ASD-affected individuals, disrupt stimulus-dependent enhancer activation, indicating a potential non-coding mechanism contributing to ASD risk. - Overall, the findings support a model in which recruitment of FOS and BAF to enhancers is required for activity-dependent gene expression in human neurons, and disruption of this process—via ARID1A loss or non-coding motif variants—may contribute to ASD pathogenesis. - The authors conclude that genetic variation in FOS/BAF-bound regulatory elements can impact BAF function and neuronal transcriptional programs downstream of FOS, linking chromatin remodeling, transcription factor binding, and ASD-associated gene regulation.
## Clinical Analysis & Structured Key Points
The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs | bioRxiv Skip to main content New Results The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs View ORCID Profile Sara K Trowbridge , View ORCID Profile GiHun Choi , View ORCID Profile Ava C Carter , View ORCID Profile Jillian E Petrocelli , View ORCID Profile Josephine E Robb , View ORCID Profile Gabriel T Koreman , Siwei Chen , View ORCID Profile Ryan N Doan , Christopher P Davis , David A Harmin , View ORCID Profile Eric C Griffith , View ORCID Profile Konrad J Karczewski , View ORCID Profile J Wade Harper , View ORCID Profile Michael E Greenberg doi: https://doi.org/10.64898/2026.08.25.747063 Sara K Trowbridge 1 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sara K Trowbridge GiHun Choi 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for GiHun Choi Ava C Carter 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ava C Carter Jillian E Petrocelli 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jillian E Petrocelli Josephine E Robb 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Josephine E Robb Gabriel T Koreman 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gabriel T Koreman Siwei Chen 3 Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ryan N Doan 1 Boston Children's Hospital; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Ryan N Doan Christopher P Davis 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site David A Harmin 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Eric C Griffith 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Eric C Griffith Konrad J Karczewski 3 Broad Institute of MIT and Harvard Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Konrad J Karczewski J Wade Harper 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for J Wade Harper Michael E Greenberg 2 Harvard Medical School; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michael E Greenberg For correspondence: michael_greenberg{at}hms.harvard.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract The BAF chromatin remodeling complex is critical to normal brain development, and rare variants within genes encoding BAF subunits are a common genetic cause of neurodevelopmental disorders, including autism spectrum disorder (ASD). Yet the factors that direct BAF binding across the neuronal genome, the human neuronal gene programs that are regulated by BAF, and the mechanisms whereby BAF subunit perturbation leads to ASD are not known. We find that BAF binds with the activity-dependent transcription factor FOS to distal regulatory regions that, in response to neuronal activity, undergo chromatin opening and show evidence of enhancer activation. Knock-out of ARID1A, a BAF subunit implicated in ASD, leads to decreased chromatin accessibility at FOS/BAF binding sites concomitant with decreased expression of nearby activity-regulated ASD-associated genes. Additionally, we find that the FOS binding motif in FOS/BAF-bound regions is highly constrained in the human population, and that rare variants in this motif in ASD-affected individuals disrupt stimulus-dependent enhancer activation. This suggests that genetic variation in FOS/BAF-bound regions contributes to ASD pathogenesis, due to an inability to recruit FOS and BAF to enhancers to promote gene expression. Together, our findings highlight a role for BAF in mediating neuronal transcriptional programs downstream of FOS and reveal a mechanism by which non-coding variants may impact BAF function and contribute to risk for ASD. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared National Institute of Neurological Disorders and Stroke, https://ror.org/01s5ya894 , R25NS070682 , K08NS130150 , L40NS134078 , R35NS143029 Simons Foundation, https://ror.org/01cmst727 , 703333 Paul G. Allen Family Foundation, https://ror.org/01degd278 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted August 27, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs Sara K Trowbridge , GiHun Choi , Ava C Carter , Jillian E Petrocelli , Josephine E Robb , Gabriel T Koreman , Siwei Chen , Ryan N Doan , Christopher P Davis , David A Harmin , Eric C Griffith , Konrad J Karczewski , J Wade Harper , Michael E Greenberg bioRxiv 2026.08.25.747063; doi: https://doi.org/10.64898/2026.08.25.747063 Share This Article: Copy Citation Tools The BAF complex works with FOS to regulate human neuronal activity-dependent ASD-associated gene programs Sara K Trowbridge , GiHun Choi , Ava C Carter , Jillian E Petrocelli , Josephine E Robb , Gabriel T Koreman , Siwei Chen , Ryan N Doan , Christopher P Davis , David A Harmin , Eric C Griffith , Konrad J Karczewski , J Wade Harper , Michael E Greenberg bioRxiv 2026.08.25.747063; doi: https://doi.org/10.64898/2026.08.25.747063 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7937) Biochemistry (18552) Bioengineering (14709) Bioinformatics (43944) Biophysics (22355) Cancer Biology (19480) Cell Biology (26651) Clinical Trials (138) Developmental Biology (13851) Ecology (20788) Epidemiology (2067) Evolutionary Biology (25214) Genetics (16049) Genomics (23314) Immunology (18508) Microbiology (42054) Molecular Biology (17874) Neuroscience (92484) Paleontology (691) Pathology (2955) Pharmacology and Toxicology (5046) Physiology (8026) Plant Biology (15820) Scientific Communication and Education (2090) Synthetic Biology (4520) Systems Biology (10147) Zoology (2367)
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