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Principles of 3D compartmentalization of the human genome.

ABSTRACT: Chromatin is organized in the nucleus via CTCF loops and compartmental domains. Here, we compare different cell types to identify distinct paradigms of compartmental domain formation in human tissues. We identify and quantify compartmental forces correlated with histone modifications characteristic of transcriptional activity and previously underappreciated roles for distinct compartmental domains correlated with the presence of H3K27me3 and H3K9me3, respectively. We present a computer simulation model capable of predicting compartmental organization based on the biochemical characteristics of independent chromatin features. Using this model, we show that the underlying forces responsible for compartmental domain formation in human cells are conserved and that the diverse compartmentalization patterns seen across cell types are due to differences in chromatin features. We extend these findings to Drosophila to suggest that the same principles are at work beyond humans. These results offer mechanistic insights into the fundamental forces driving the 3D organization of the genome.

SUBMITTER: Nichols MH

PROVIDER: S-EPMC8265014 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLike most hospitals, our hospital experienced COVID-19 pandemic-related supply chain shortages. Our additive manufacturing lab's capacity to offset these shortages was soon overwhelmed, leading to a need to improve the efficiency of our existing workflow. We undertook a work system analysis guided by the Systems Engineering Initiative for Patient Safety (SEIPS) construct which is based on human factors and quality improvement principles. Our objective was to understand the inefficiencies in project submission, review, and acceptance decisions, and make systematic improvements to optimize lab operations.MethodsContextual inquiry (interviews and workflow analysis) revealed suboptimal characteristics of the system, specifically, reliance on a single person to facilitate work and, at times, fractured communication with project sponsors, with root causes related to the project intake and evaluation process as identified through SEIPS tools. As interventions, the analysis led us to: 1) enhance an existing but underused project submission form, 2) design and implement an internal project scorecard to standardize evaluation of requests, and 3) distribute the responsibility of submission evaluation across lab members. We implemented these interventions in May 2021 for new projects and compare them to our baseline February 1, 2018 through - April 30, 2021 performance (1184 days).ResultsAll project requests were submitted using the enhanced project submission form and all received a standardized evaluation with the project scorecard. Prior to interventions, we completed 35/79 (44%) of projects, compared to 12/20 (60%) of projects after interventions were implemented. Time to review new submissions was reduced from an average of 58 days to 4 days. A more distributed team responsibility structure permitted improved workflow with no increase in staffing, allowing the Lab Manager to devote more time to engineering rather than administrative/decision tasks.ConclusionsBy optimizing our workflows utilizing a human factors approach, we improved the work system of our additive manufacturing lab to be responsive to the urgent needs of the pandemic. The current workflow provides insights for labs aiming to meet the growing demand for point-of-care manufacturing.

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Principles of 3D compartmentalization of the human genome.

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