SRF promotes long-range chromatin loop formation and stem cell pluripotency

• Published in: Cell reports (Cambridge) 2024-10, Vol.43 (10), p.114846, Article 114846
• Main Authors: Tsaytler, Pavel, Blaess, Gaby, Scholze-Wittler, Manuela, Meierhofer, David, Wittler, Lars, Koch, Frederic, Herrmann, Bernhard G.
• Format: Article
• Language: English
• Subjects: chromatin loops; chromatin organization; CTCF; long-range contact regulation; NANOG; OSN enhancers; pluripotency; SOX2; SRF; TAD insulation
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114846

Serum response factor (SRF) is a transcription factor essential for cell proliferation, differentiation, and migration and is required for primitive streak and mesoderm formation in the embryo. The canonical roles of SRF are mediated by a diverse set of context-dependent cofactors. Here, we show that SRF physically interacts with CTCF and cohesin subunits at topologically associating domain (TAD) boundaries and loop anchors. SRF promotes long-range chromatin loop formation and contributes to TAD insulation. In embryonic stem cells (ESCs), SRF associates with SOX2 and NANOG and contributes to the formation of three-dimensional (3D) pluripotency hubs. Our findings reveal additional roles of SRF in higher-order chromatin organization. [Display omitted] •SRF interacts and co-localizes with CTCF and cohesin throughout the genome•SRF promotes enhancer loop formation and contributes to TAD boundary insulation•SRF enforces high-level expression of the pluripotency factors Sox2 and Nanog Tsaytler et al. discovered co-localization of the serum response factor (SRF) with CTCF and the cohesin subunit RAD21 at most of its binding sites. SRF depletion revealed a new role of SRF in TAD insulation and enhancer loop formation as well as the control of pluripotency factors in ESCs.