Liquid-liquid phase separation of lamin drives altered chromatin organisation in cardiomyopathic mutations of lamin A

Name: Liquid-liquid phase separation of lamin drives altered chromatin organisation in cardiomyopathic mutations of lamin A
Creator: figshare
Published: 2025-05-14T10:19:33+08:00

DataCite Commons2025-06-06 更新2025-09-08 收录

染色体三维结构

核纤层相互作用

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https://figshare.com/articles/dataset/LaminChromatin/29063591 数据链接链接失效反馈

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# Coarse-Grained Chromatin–Lamin Simulation This repository describes the setup and simulation details for a coarse-grained model of chromatin and lamin interactions, inspired by experimental data from the mouse **C2C12** cell line (GRCm38/mm10). --- ## 🧬 Coarse-Grained Model of Chromatin and Lamins ### Chromatin Model - A 10.7 Mbp region of **mouse chromosome 18** was modeled.- Chromatin is represented as a **heteropolymer chain** with: - **2140 beads** - Each bead corresponds to **5 kbp** of DNA (~25 nucleosomes) - Bead diameter: `σ` - Beads are classified as: - **Euchromatin (EC)** - **Heterochromatin (HC)** Classification is based on **H3K9me3 ChIP-seq** enrichment [[Beyer et al., 2016]](https://doi.org/10.1016/j.celrep.2016.06.081). #### HC Fraction Calculation (`f_HC`)- Chromosome segments were binned into **2140 × 5kb** windows.- A bin is HC if ≥ 50% of it is enriched in H3K9me3.- `f_HC` = fraction of HC beads out of 2140. ### Random Block Copolymer Control - Segment = block of 20 consecutive beads.- Beads randomly labeled EC or HC based on `f_HC`. ### Lamin Model - Lamins are modeled as coarse-grained particles with: - Diameter: `σ_L = σ / 2` - Total count: **2000 lamin particles** --- ## 🧱 Simulation Box - Dimensions: `20σ × 20σ × 35σ` (x, y, z)- **Periodic** boundary in `x`, `y`; **fixed** boundary in `z` - Simulates confinement near the **nuclear envelope** ### Volume Fractions Chromatin:```V_chromatin / V_box = (2140 × 4πσ³/24) / (14000σ³) ≈ 0.08``` Lamin:```V_lamin / V_box = (2000 × 4πσ³/192) / (14000σ³) ≈ 0.01``` --- ## ⚙️ Interaction Potentials The **total energy** of the system is: ```U = Σ_{i=1}^{N-1} U_spring(|r_{i+1}-r_i|) + Σ_{i=1}^{N-1} Σ_{j=i+1}^{N} U_pair(|r_j - r_i|)``` ### 1. FENE Spring Potential Used for polymer backbone connectivity:```U_spring(r) = -½ k R₀² ln[1 - (r / R₀)²]```- `k = 30 k_B T / σ²`- `R₀ = 1.6σ` ### 2. Nonbonded Interactions Depending on the context, either **Lennard-Jones (LJ)** or **WCA** (purely repulsive LJ) potential is used. #### Lennard-Jones (LJ) ```U_LJ(r) = 4ε[(σ/r)^12 - (σ/r)^6], r < 1.8σ 0, r ≥ 1.8σ``` #### Weeks-Chandler-Andersen (WCA) ```U_WCA(r) = 4ε[(σ/r)^12 - (σ/r)^6] + E_cut, r < 1.12σ 0, r ≥ 1.12σ``` Where the shift:```E_cut = -4ε[(σ/r_c)^12 - (σ/r_c)^6], r_c = 1.12σ``` --- ## 🧲 Boundary Interactions - `z = +17.5σ` (upper): **Attractive LJ** interaction (nuclear membrane with lamin)- `z = -17.5σ` (lower): **Completely repulsive** for all particles --- ## 📋 Table of Interaction Parameters | Interaction Type | Potential Used | Notes ||-------------------------|----------------|-------|| Chromatin–Chromatin | LJ / WCA | EC–EC, HC–HC, HC–EC types || Lamin–Lamin | LJ / WCA | Short-range attraction || Chromatin–Lamin | LJ / WCA | HC-specific attractive interaction || Wall (Top)–Lamin | LJ | Simulates membrane || Wall (Bottom)–All | WCA | No penetration | --- ## 📚 Reference Beyer, T. A., et al. (2016). *Canonical histone marks are predictive of chromatin architecture*. Cell Reports, 17(2), 307-320. https://doi.org/10.1016/j.celrep.2016.06.081

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创建时间：

2025-05-14