BAF complexes maintain accessibility at stimulus-responsive chromatin and are required for transcriptional stimulus responses
Posted on: 8 August 2026
Preprint posted on 21 March 2026
''BAF is the chromatin gatekeeper that turns cellular signals into gene activity''.
Selected by Dina Kabbara
Categories: cell biology, genomics, molecular biology, systems biology
Background
Cells are constantly exposed to external signals such as cytokines, hormones, and stress-related cues. These signals activate intracellular pathways that ultimately lead to changes in gene expression. However, only specific genes respond in a given cell type, raising the question of how cells maintain the ability, or “competence,” to respond appropriately (Heinz et al., 2010; Natoli et al., 2019).
The BAF (SWI/SNF) complex is a major ATP-dependent chromatin remodeler that regulates nucleosome positioning and chromatin accessibility (Clapier et al., 2017). It uses energy to adjust DNA packaging and thereby controls whether regulatory regions are accessible to transcription factors (Thurman et al., 2012; Clapier et al., 2017).
Mutations in BAF subunits are frequently observed in cancer and developmental disorders, highlighting their biological importance (Lee et al., 2012; Valencia et al., 2023). However, it remains unclear whether BAF primarily supports active transcription or whether it also maintains regulatory elements in a state that enables future activation (Schick et al., 2021).
To address this, the authors of this preprint acutely inhibited the ATPase subunits SMARCA2 and SMARCA4 in GM12878 lymphoblastoid cell lines and profiled chromatin accessibility and transcriptional responses following stimulation. Their findings support the model shown in preprint Figure 6, in which continuous BAF activity maintains accessibility at primed enhancers and is required for effective stimulus-induced gene activation.
Figure 6: Model for BAF regulation of stimulus-responsive transcription through maintenance of primed enhancer accessibility. (A) BAF complexes sustain chromatin accessibility at primed enhancers in a continuous manner. Following cellular stimulation, signal-dependent transcription factors engage these accessible enhancers, enabling their activation and driving the induction of downstream target genes (bottom). (B) When BAF activity is reduced, primed enhancers progressively lose accessibility. This widespread chromatin closure compromises enhancer activation upon stimulation, ultimately leading to impaired transcriptional responses to external cues (bottom).
Key Findings
BAF inhibition causes rapid genome-wide loss of chromatin accessibility
Acute BAF inhibition caused a rapid, genome-wide loss of chromatin accessibility, as measured by ATAC-seq, a technique that identifies open regions of DNA. Enhancers, which are distal regulatory DNA elements that boost gene expression, were more susceptible than promoters (gene-starting regions) or insulator regions (DNA boundaries that prevent unwanted interactions). Overall, over 52,000 accessible regions lost accessibility, and approximately 71% of enhancers were affected within 30 minutes (preprint Figure 1).
BAF supports cell identity and regulatory enhancer programs
BAF selectively supports cell identity and adaptive regulatory programs, as shown by computational analyses of chromatin features and transcription factor binding. These analyses revealed that BAF-dependent enhancers are enriched for lineage-defining and stimulus-responsive transcription factors, including AP-1, RUNX3, and PU.1, which regulate gene expression programs involved in cell identity and environmental responses (preprint Figure 2).
Primed enhancers are most dependent on BAF activity
Among enhancer subclasses, primed enhancers, enhancers that are already accessible but not yet fully active, allowing them to respond rapidly to future signals, showed the highest reliance on BAF. About 75% of primed enhancers lost accessibility after BAF inhibition, indicating that continuous chromatin remodeling is required to maintain these poised regulatory elements in a transcription-ready state (preprint Figure 3).
BAF is required for stimulus-responsive transcriptional activation
Functionally, BAF inhibition significantly reduced transcriptional responses to external stimuli such as interferon-γ (an immune signaling molecule) and dexamethasone (a synthetic anti-inflammatory hormone) by preventing the normal stimulus-induced increase in enhancer accessibility. RNA sequencing showed that most stimulus-responsive genes failed to activate properly, demonstrating that BAF is necessary not only for basal chromatin maintenance but also for dynamic gene activation in response to environmental signals (preprint Figures 4–5).
What I like about this preprint
This preprint asks a simple but important question: what determines a cell’s ability to respond to a signal? I like that it shifts attention away from signaling pathways and toward the chromatin landscape that makes responses possible.
I was drawn to this study because, despite the system’s complexity, it feels instantly intuitive. You can practically see enhancers losing accessibility and see that collapse mirrored in the failure of gene induction, thanks to the figures’ exceptional ability to translate an abstract regulatory process into something visually tangible.
Additionally, I liked how the work reinterprets BAF as a mechanism that actively maintains cellular preparedness rather than just a general chromatin “maintenance” element. The concept of a “poised but responsive” enhancer landscape is highly appealing, since it depicts chromatin as a functional state that influences future potential rather than as a static layer.
In a broader sense, the research aligns well with current conversations in chromatin biology on the functions of remodeling complexes beyond baseline transcription. Rather, they seem to determine whether a cell is even capable of mounting a suitable transcriptional response to a signal.
Future directions
Future work should explore whether additional chromatin remodeling complexes similarly maintain enhancer competence and whether specific BAF subunit compositions confer pathway-specific regulatory functions. Further investigation into how disruption of this system contributes to aberrant cellular responses may help clarify its role in diseases such as cancer, inflammation, and developmental disorders.
More broadly, these findings support a model in which chromatin acts as an active gatekeeper of cellular responsiveness, determining whether external signals are effectively translated into gene expression. This framework highlights chromatin remodeling as a potential therapeutic target for modulating cellular responses in disease contexts.
Questions for authors
Q1: In this preprint, BAF-dependent enhancers are enriched for lineage- and stimulus-specific transcription factors such as AP-1, RUNX3, and PU.1, suggesting functional coupling between BAF activity and transcription factor programs in shaping enhancer responsiveness. How do distinct BAF subunit compositions interact with transcription factors to define enhancer and stimulus-response specificity?
Q2: How do signaling pathway crosstalk and cooperative or antagonistic transcription factor networks operating at BAF-accessible enhancers determine whether transcription is productively activated or repressed?”
References
- Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010). Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Molecular Cell, 38(4), 576–589. https://doi.org/10.1016/j.molcel.2010.05.004
- Natoli, G., & Ostuni, R. (2019). Adaptation and memory in immune responses. Nature Immunology, 20(7), 783–792. https://doi.org/10.1038/s41590-019-0399-9
- Clapier, C. R., Iwasa, J., Cairns, B. R., & Peterson, C. L. (2017). Mechanisms of action and regulation of ATP-dependent chromatin-remodeling complexes. Nature Reviews Molecular Cell Biology, 18(7), 407–422. https://doi.org/10.1038/nrm.2017.26
- Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., Garg, K., John, S., Sandstrom, R., Bates, D., Boatman, L., Canfield, T. K., Diegel, M., Dunn, D., Ebersol, A. K., … Stamatoyannopoulos, J. A. (2012). The accessible chromatin landscape of the human genome. Nature, 489(7414), 75–82. https://doi.org/10.1038/nature11232
- Lee, R. S., Stewart, C., Carter, S. L., Ambrogio, L., Cibulskis, K., Sougnez, C., Lawrence, M. S., Auclair, D., Mora, J., Golub, T. R., Biegel, J. A., Getz, G., & Roberts, C. W. M. (2012). A remarkably simple genome underlies highly malignant pediatric rhabdoid cancers. Journal of Clinical Investigation, 122(8), 2983–2988. https://doi.org/10.1172/jci64400
- Valencia, A. M., Sankar, A., van der Sluijs, P. J., Satterstrom, F. K., Fu, J., Talkowski, M. E., Vergano, S. A., Santen, G. W., & Kadoch, C. (2023). Landscape of MSWI/SNF chromatin remodeling complex perturbations in neurodevelopmental disorders. Nature Genetics, 55(8), 1400–1412. https://doi.org/10.1038/s41588-023-01451-6
- Schick, S., Grosche, S., Kohl, K. E., Drpic, D., Jaeger, M. G., Marella, N. C., Imrichova, H., Lin, J.-M. G., Hofstätter, G., Schuster, M., Rendeiro, A. F., Koren, A., Petronczki, M., Bock, C., Müller, A. C., Winter, G. E., & Kubicek, S. (2021). Acute Baf perturbation causes immediate changes in chromatin accessibility. Nature Genetics, 53(3), 269–278. https://doi.org/10.1038/s41588-021-00777-3
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| List by | Theodora Stougiannou et al. |
BSDB Spring Meeting: Molecules to Morphogenesis
The British Society for Developmental Biology (BSDB) Spring Meeting Molecules to Morphogenesis was held from 23–26 March 2026 at the University of Warwick (UK). This meeting brought together a vibrant community of researchers to discuss how molecular mechanisms are integrated across scales to drive morphogenesis, spanning diverse model systems and approaches. This preList contains preprints by presenters from the talk and poster sessions at the meeting. Please do get in touch at preLights@biologists.com if you notice any relevant preprints that we may have missed.
| List by | Ingrid Tsang |
Keystone Symposium on Stem Cell Models in Embryology 2026
The Keystone Symposium on Stem Cell Models in Embryology, 2026, was organised by Jun Wu (UT Southwestern), Jianping Fu (University of Michigan) and Miki Ebisuya (TU Dresden) and held at Asilomar Conference Grounds in California (US). The meeting discussed recent advances made in establishing stem-cell-based embryo models, what fundamental insights into developmental processes have been gleaned from them, as well as how they are beginning to be applied more widely. This prelist contains preprints by presenters at the talk and poster sessions at the conference, which our Reviews Editor in attendance spotted. Please do reach out to preLights@biologists.com if you notice any that we’ve missed.
| List by | Ingrid Tsang |
SciELO preprints – From 2025 onwards
SciELO has become a cornerstone of open, multilingual scholarly communication across Latin America. Its preprint server, SciELO preprints, is expanding the global reach of preprinted research from the region (for more information, see our interview with Carolina Tanigushi). This preList brings together biological, English language SciELO preprints to help readers discover emerging work from the Global South. By highlighting these preprints in one place, we aim to support visibility, encourage early feedback, and showcase the vibrant research communities contributing to SciELO’s open science ecosystem.
| List by | Carolina Tanigushi |
October in preprints – DevBio & Stem cell biology
Each month, preLighters with expertise across developmental and stem cell biology nominate a few recent developmental and stem cell biology (and related) preprints they’re excited about and explain in a single paragraph why. Short, snappy picks from working scientists — a quick way to spot fresh ideas, bold methods and papers worth reading in full. These preprints can all be found in the October preprint list published on the Node.
| List by | Deevitha Balasubramanian et al. |
October in preprints – Cell biology edition
Different preLighters, with expertise across cell biology, have worked together to create this preprint reading list for researchers with an interest in cell biology. This month, most picks fall under (1) Cell organelles and organisation, followed by (2) Mechanosignaling and mechanotransduction, (3) Cell cycle and division and (4) Cell migration
| List by | Matthew Davies et al. |
September in preprints – Cell biology edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading list. This month, categories include: (1) Cell organelles and organisation, (2) Cell signalling and mechanosensing, (3) Cell metabolism, (4) Cell cycle and division, (5) Cell migration
| List by | Sristilekha Nath et al. |
June in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: (1) Cell organelles and organisation (2) Cell signaling and mechanosensation (3) Genetics/gene expression (4) Biochemistry (5) Cytoskeleton
| List by | Barbora Knotkova et al. |
May in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) Biochemistry/metabolism 2) Cancer cell Biology 3) Cell adhesion, migration and cytoskeleton 4) Cell organelles and organisation 5) Cell signalling and 6) Genetics
| List by | Barbora Knotkova et al. |
Keystone Symposium – Metabolic and Nutritional Control of Development and Cell Fate
This preList contains preprints discussed during the Metabolic and Nutritional Control of Development and Cell Fate Keystone Symposia. This conference was organized by Lydia Finley and Ralph J. DeBerardinis and held in the Wylie Center and Tupper Manor at Endicott College, Beverly, MA, United States from May 7th to 9th 2025. This meeting marked the first in-person gathering of leading researchers exploring how metabolism influences development, including processes like cell fate, tissue patterning, and organ function, through nutrient availability and metabolic regulation. By integrating modern metabolic tools with genetic and epidemiological insights across model organisms, this event highlighted key mechanisms and identified open questions to advance the emerging field of developmental metabolism.
| List by | Virginia Savy, Martin Estermann |
April in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry/metabolism 2) cell cycle and division 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) (epi)genetics
| List by | Vibha SINGH et al. |
Biologists @ 100 conference preList
This preList aims to capture all preprints being discussed at the Biologists @100 conference in Liverpool, UK, either as part of the poster sessions or the (flash/short/full-length) talks.
| List by | Reinier Prosee, Jonathan Townson |
February in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry and cell metabolism 2) cell organelles and organisation 3) cell signalling, migration and mechanosensing
| List by | Barbora Knotkova et al. |
Community-driven preList – Immunology
In this community-driven preList, a group of preLighters, with expertise in different areas of immunology have worked together to create this preprint reading list.
| List by | Felipe Del Valle Batalla et al. |
January in preprints – the CellBio edition
A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. This month, categories include: 1) biochemistry/metabolism 2) cell migration 3) cell organelles and organisation 4) cell signalling and mechanosensing 5) genetics/gene expression
| List by | Barbora Knotkova et al. |
2024 Hypothalamus GRC
This 2024 Hypothalamus GRC (Gordon Research Conference) preList offers an overview of cutting-edge research focused on the hypothalamus, a critical brain region involved in regulating homeostasis, behavior, and neuroendocrine functions. The studies included cover a range of topics, including neural circuits, molecular mechanisms, and the role of the hypothalamus in health and disease. This collection highlights some of the latest advances in understanding hypothalamic function, with potential implications for treating disorders such as obesity, stress, and metabolic diseases.
| List by | Nathalie Krauth |
BSCB-Biochemical Society 2024 Cell Migration meeting
This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.
| List by | Reinier Prosee |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
CSHL 87th Symposium: Stem Cells
Preprints mentioned by speakers at the #CSHLsymp23
| List by | Alex Eve |
9th International Symposium on the Biology of Vertebrate Sex Determination
This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.
| List by | Martin Estermann |
Alumni picks – preLights 5th Birthday
This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.
| List by | Sergio Menchero et al. |
CellBio 2022 – An ASCB/EMBO Meeting
This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.
| List by | Nadja Hümpfer et al. |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
FENS 2020
A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020
| List by | Ana Dorrego-Rivas |
ECFG15 – Fungal biology
Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome
| List by | Hiral Shah |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
| List by | Rob Hynds |
MitoList
This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.
| List by | Sandra Franco Iborra |
Also in the systems biology category:
2024 Hypothalamus GRC
This 2024 Hypothalamus GRC (Gordon Research Conference) preList offers an overview of cutting-edge research focused on the hypothalamus, a critical brain region involved in regulating homeostasis, behavior, and neuroendocrine functions. The studies included cover a range of topics, including neural circuits, molecular mechanisms, and the role of the hypothalamus in health and disease. This collection highlights some of the latest advances in understanding hypothalamic function, with potential implications for treating disorders such as obesity, stress, and metabolic diseases.
| List by | Nathalie Krauth |
‘In preprints’ from Development 2022-2023
A list of the preprints featured in Development's 'In preprints' articles between 2022-2023
| List by | Alex Eve, Katherine Brown |
EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)
A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.
| List by | Alex Eve |
Single Cell Biology 2020
A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.
| List by | Alex Eve |
ASCB EMBO Annual Meeting 2019
A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)
| List by | Madhuja Samaddar et al. |
EMBL Seeing is Believing – Imaging the Molecular Processes of Life
Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019
| List by | Dey Lab |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
| List by | Alexa Sadier |