Advances in the multimodal analysis of the 3D chromatin structure and gene regulation

Recent studies have demonstrated that the three-dimensional conformation of the chromatin plays a crucial role in gene regulation, with aberrations potentially leading to various diseases. Advanced methodologies have revealed a link between the chromatin conformation and biological function. This review divides these methodologies into sequencing-based and imaging-based methodologies, tracing their development over time. We particularly highlight innovative techniques that facilitate the simultaneous mapping of RNAs, histone modifications, and proteins within the context of the 3D architecture of chromatin. This multimodal integration substantially improves our ability to establish a robust connection between the spatial arrangement of molecular components in the nucleus and their functional roles. Achieving a comprehensive understanding of gene regulation requires capturing diverse data modalities within individual cells, enabling the direct inference of functional relationships between these components. In this context, imaging-based technologies have emerged as an especially promising approach for gathering spatial information across multiple components in the same cell. Understanding how genes work and interact within our cells is key to understanding biology and disease. This review looks at the latest methods for analyzing the 3D structure of our genome, focusing on sequencing, and microscopy techniques. It shows how these technologies let us see our DNA structure in 3D and understand how this affects gene activity and cell functions. The authors aim to provide a fuller picture of how DNA's spatial arrangement affects its function by combining different methods. They discuss methods that can concurrently map the landscape of chromatin structure along with the transcriptomic, proteomic, and epigenetic landscape, all critical for biological functions. Such a comprehensive perspective is vital for accurately unraveling the complex interactions and regulatory mechanisms within the nucleus, thereby enhancing our understanding of the functional significance of 3D chromatin architecture.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.