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Creators/Authors contains: "Li, Zilong"

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  1. Abstract

    The structure and dynamics of the eukaryotic genome are intimately linked to gene regulation and transcriptional activity. Many chromosome conformation capture experiments like Hi-C have been developed to detect genome-wide contact frequencies and quantify loop/compartment structures for different cellular contexts and time-dependent processes. However, a full understanding of these events requires explicit descriptions of representative chromatin and chromosome configurations. With the exponentially growing amount of data from Hi-C experiments, many methods for deriving 3D structures from contact frequency data have been developed. Yet, most reconstruction methods use polymer models with low resolution to predict overall genome structure. Here we present a Brownian Dynamics (BD) approach termed Hi-BDiSCO for producing 3D genome structures from Hi-C and Micro-C data using our mesoscale-resolution chromatin model based on the Discrete Surface Charge Optimization (DiSCO) model. Our approach integrates reconstruction with chromatin simulations at nucleosome resolution with appropriate biophysical parameters. Following a description of our protocol, we present applications to the NXN, HOXC, HOXA and Fbn2 mouse genes ranging in size from 50 to 100 kb. Such nucleosome-resolution genome structures pave the way for pursuing many biomedical applications related to the epigenomic regulation of chromatin and control of human disease.

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  2. Free, publicly-accessible full text available August 1, 2024
  3. Abstract

    Drosophilais a powerful genetic model system for cardiovascular studies. Recently, optogenetic pacing tools have been developed to controlDrosophilaheart rhythm noninvasively with blue light, which has a limited penetration depth. Here we developed both a red-light sensitive opsin expressingDrosophilasystem and an integrated red-light stimulation and optical coherence microscopy (OCM) imaging system. We demonstrated noninvasive control ofDrosophilacardiac rhythms using a single light source, including simulated tachycardia in ReaChR-expressing flies and bradycardia and cardiac arrest in halorhodopsin (NpHR)-expressing flies at multiple developmental stages. By using red excitation light, we were able to pace flies at higher efficiency and with lower power than with equivalent blue light excitation systems. The recovery dynamics after red-light stimulation of NpHR flies were observed and quantified. The combination of red-light stimulation, OCM imaging, and transgenicDrosophilasystems provides a promising and easily manipulated research platform for noninvasive cardiac optogenetic studies.

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  4. null (Ed.)