liangruf

• Tiusanen, Ville; Patel, Divyeshkumar Amrubthai; Xia, Jihan; Xu, Chi; Datta, Subhamoy & Yun, Ji [Show all 13 contributors for this article] (2026). Classical enhancers couple cis-regulatory logic with transcriptional condensates and 3D genome architecture. bioRxiv - the preprint server for biology. doi: 10.64898/2026.01.23.701252. Full text in Research Archive Show summary

  Abstract Deciphering the regulatory logic of enhancers remains a central question in understanding cell- and tissue-specific gene expression in multicellular organisms. This is particularly pertinent at multipartite enhancer clusters such as super-enhancers, where multiple enhancers contribute to the expression of a single gene. Gene expression has been studied largely through sequence-dependent recruitment of transcription factors (TF) and co-activators, whereas 3D chromatin structure has been attributed to architectural proteins such as cohesion and CTCF 1–3 . However, the contribution of DNA sequence encoded in enhancers to shaping higher-order genome organization remains poorly understood. Here we show that classical enhancers, embedded within multipartite super-enhancer structures, act as determinant regulatory elements that initiate the gene regulatory cascade by linking DNA sequence recognition to 3D chromatin architecture. Classical enhancers are more evolutionarily conserved and display stronger regulatory activity than facilitator elements, which lack intrinsic enhancer activity but potentiate classical enhancer function. We show that classical enhancers are selectively bound by specific TFs with strong intrinsically disordered regions, such as NFE2L2 in liver cancer cells, capable of driving transcriptional condensate formation through phase separation. NFE2L2 depletion reduced enhancer activity and induced widespread chromatin reorganization, characterized by increased cohesin and CTCF occupancy at super-enhancer boundaries and beyond. This “cohesin clogging” impaired DNA loop extrusion, led to formation of smaller topologically associated domains, and weakened enhancer–promoter contacts. These findings highlight that sequence-specific TFs have multifaceted roles beyond transcriptional control, establishing a direct mechanistic link between enhancer sequence, TF binding, condensate formation, and 3D genome organization, with the regulatory logic being encoded in the DNA sequence itself.

• Tuohinto, Krista; Graus, Matthew S.; Staab, Peyton; Tiusanen, Ville; Fei, Liangru & Pradhan, Susav [Show all 20 contributors for this article] (2025). Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence. bioRxiv - the preprint server for biology. doi: 10.1101/2025.06.28.662102. Full text in Research Archive Show summary

  Abstract Kaposi’s sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1—genetically or pharmacologically—leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.

• Fei, Liangru; Zhang, Kaiyang; Hautaniemi, Sampsa & Sahu, Biswajyoti (2024). Protocol to identify defined reprogramming factor expression using a factor-indexing single-nuclei multiome sequencing approach. STAR Protocols. 5(3). doi: 10.1016/j.xpro.2024.103148. Full text in Research Archive Show summary

  Ectopic expression of lineage-specific transcription factors (TFs) of another cell type can induce cell fate reprogramming. However, the heterogeneity of reprogramming cells has been a challenge for data interpretation and model evaluation. Here, we present a protocol to characterize cells expressing defined factors during direct cell reprogramming using a factor-indexing approach based on single-nuclei multiome sequencing (FI-snMultiome-seq). We describe the steps for barcoding TFs, converting human fibroblasts to pancreatic ductal-like cells using defined TFs, and preparing library for FI-snMultiome-seq analysis. For complete details on the use and execution of this protocol, please refer to Fei et al.1

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