Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.
7 affiliations
- 1National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
- 2Transgenic Core, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
- 3Genome Technology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD, USA.
- 4Department of Physics and Department of Anatomy and Cell Biology, The George Washington University, Washington, DC, USA.
- 5Laboratory of Muscle Stem Cells and Gene Regulation, NIAMS, NIH, Bethesda, MD, USA.
- 6National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, USA. [email protected].
- 7National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD, USA. [email protected].
Abstract
Transcription factors (TFs) bind to enhancers and recruit H3K4me1 methyltransferase KMT2D, chromatin remodeler cBAF, and H3K27 acetyltransferase p300 to activate transcription. However, the role of chromatin modifiers in regulating de novo binding of TFs on enhancers remains unclear. Using a robust nuclear translocation system, we show that the muscle lineage-determining TF MyoD binds to chromatin pervasively within one hour, with half of induced MyoD binding sites co-occupied by KMT2D, cBAF, and p300. On the majority of these MyoD⁺ enhancers, acute depletion of KMT2D or short-term inhibition of cBAF or p300 enzymatic activity markedly reduces de novo binding of MyoD as well as that of KMT2D, cBAF, and p300. On enhancers with intact MyoD binding despite these perturbations, we observe cooperative recruitment among chromatin modifiers. Similar interdependent relationships are observed between the signal-dependent TF Glucocorticoid Receptor and KMT2D, cBAF, and p300. Together, our findings show that chromatin modifiers are not only downstream effectors but also required for de novo binding of TFs on enhancers, refining a model of enhancer establishment as a process governed by functional cooperation rather than a strict hierarchy.
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BibTeX
@article{van2026chromatin,
title = {{Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.}},
author = {Hieu T Van and Young-Kwon Park and Danyang Wan and Chengyu Liu and Shamima Islam and Stefania Dell'Orso and Weiqun Peng and Vittorio Sartorelli and Ji-Eun Lee and Kai Ge},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77757-w},
url = {https://europepmc.org/article/MED/42875463},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chromatin modifiers KMT2D, cBAF, and p300 cooperatively facilitate de novo binding of transcription factors on enhancers.
AU - Hieu T Van
AU - Young-Kwon Park
AU - Danyang Wan
AU - Chengyu Liu
AU - Shamima Islam
AU - Stefania Dell'Orso
AU - Weiqun Peng
AU - Vittorio Sartorelli
AU - Ji-Eun Lee
AU - Kai Ge
PY - 2026
DA - 2026/09/15
JO - Nature communications
DO - 10.1038/s41467-026-77757-w
UR - https://europepmc.org/article/MED/42875463
AB - Transcription factors (TFs) bind to enhancers and recruit H3K4me1 methyltransferase KMT2D, chromatin remodeler cBAF, and H3K27 acetyltransferase p300 to activate transcription. However, the role of chromatin modifiers in regulating de novo binding of TFs on enhancers remains unclear. Using a robust nuclear translocation system, we show that the muscle lineage-determining TF MyoD binds to chromatin pervasively within one hour, with half of induced MyoD binding sites co-occupied by KMT2D, cBAF, and p300. On the majority of these MyoD⁺ enhancers, acute depletion of KMT2D or short-term inhibition of cBAF or p300 enzymatic activity markedly reduces de novo binding of MyoD as well as that of KMT2D, cBAF, and p300. On enhancers with intact MyoD binding despite these perturbations, we observe cooperative recruitment among chromatin modifiers. Similar interdependent relationships are observed between the signal-dependent TF Glucocorticoid Receptor and KMT2D, cBAF, and p300. Together, our findings show that chromatin modifiers are not only downstream effectors but also required for de novo binding of TFs on enhancers, refining a model of enhancer establishment as a process governed by functional cooperation rather than a strict hierarchy.
SN - 2041-1723
ER -