Transient alterations in nucleosome distribution and sensitivity to nuclease define the THP-1 monocyte to macrophage transition

• DOI: 10.1101/2025.02.11.637703
• Publication Date: 2025-02-16T06:35:31Z
• Authors: Jane M Benoit; Brandon D Buck; Mahdi Khadem; Hank W Bass; Jonathan H Dennis
• Keywords: Monocyte; THP1 cell line; Transient (computer programming); Nuclease

The monocyte to macrophage transition is marked by alterations both the structure and function of genome, including changes in histone post-translational modifications, DNA methylation, 3D nuclear architecture, expression lineage specific genes. nucleosome fundamental organizational unit eukaryotic genome underpins function. However, dynamics at promoters, which are essential for transcriptional regulation, understudied cellular differentiation. We conducted high-resolution chromatin profiling promoters THP-1 cell line eight different time points spanning PMA-induced found that fewer than 10% nucleosomes within were redistributed during differentiation only a subset these associated with immediate alterations. Nucleosomes PMA-responsive genes strongly positioned prior experienced minimal thus implying existence pre-differentiation primed state. Additionally, we observed pronounced sensitivity MNase digestion one hour emergence highly resistant phenotype fully differentiated cells. resistance correlated active marks, transcription factor binding, gene expression, higher order demonstrating it useful measure Together this suggests that, unlike more stable distribution, transient may underpin new genomic functions differentiating Our results offer framework understanding how structural potentiate model use methodology widely applicable other systems.