The article "From nucleosomes to compartments: physicochemical interactions underlying chromatin organization" by Shuming Liu, Advait Athreya, Zhuohan Lao, and Bin Zhang reviews the complex interactions that govern chromatin organization. Chromatin, the packaging of DNA in eukaryotic cells, plays a crucial role in regulating genetic information access and cellular functions. The study of chromatin organization has advanced significantly through in vitro and in vivo experiments, revealing the structure of individual nucleosomes and their arrays, as well as the role of physicochemical forces in stabilizing these structures. In vivo studies have also uncovered important features such as chromatin loops, topologically associating domains (TADs), and nuclear compartments. The article highlights the significance of internucleosomal interactions, which are stronger than thermal energy and play a critical role in chromatin folding. Experimental and computational studies have quantified these interactions, showing that they are essential for the structural stability of chromatin. The strength of these interactions is influenced by factors such as DNA sequence, linker length, and histone modifications. The concept of microphase separation, driven by internucleosomal interactions, is discussed as a key mechanism for chromatin organization. This process involves the aggregation of chromatin into distinct domains and compartments, which are spatially segregated within the nucleus. Computational models have successfully recapitulated the observed chromatin organization, suggesting that intrinsic interactions between nucleosomes are sufficient to drive this process. The article also explores the role of nuclear landmarks, such as nucleoli and nuclear speckles, in modulating microphase separation. These landmarks influence chromatin organization and contribute to the functional specificity of genomic loci within the nucleus. The coupled self-assembly of the genome and nuclear landmarks is proposed as a mechanism that ensures the precise positioning of chromatin within the nucleus, leading to functional zoning rather than radial positioning. Overall, the article provides a comprehensive overview of the molecular interactions and mechanisms underlying chromatin organization, emphasizing the importance of internucleosomal interactions and the role of nuclear landmarks in shaping chromatin structure and function.The article "From nucleosomes to compartments: physicochemical interactions underlying chromatin organization" by Shuming Liu, Advait Athreya, Zhuohan Lao, and Bin Zhang reviews the complex interactions that govern chromatin organization. Chromatin, the packaging of DNA in eukaryotic cells, plays a crucial role in regulating genetic information access and cellular functions. The study of chromatin organization has advanced significantly through in vitro and in vivo experiments, revealing the structure of individual nucleosomes and their arrays, as well as the role of physicochemical forces in stabilizing these structures. In vivo studies have also uncovered important features such as chromatin loops, topologically associating domains (TADs), and nuclear compartments. The article highlights the significance of internucleosomal interactions, which are stronger than thermal energy and play a critical role in chromatin folding. Experimental and computational studies have quantified these interactions, showing that they are essential for the structural stability of chromatin. The strength of these interactions is influenced by factors such as DNA sequence, linker length, and histone modifications. The concept of microphase separation, driven by internucleosomal interactions, is discussed as a key mechanism for chromatin organization. This process involves the aggregation of chromatin into distinct domains and compartments, which are spatially segregated within the nucleus. Computational models have successfully recapitulated the observed chromatin organization, suggesting that intrinsic interactions between nucleosomes are sufficient to drive this process. The article also explores the role of nuclear landmarks, such as nucleoli and nuclear speckles, in modulating microphase separation. These landmarks influence chromatin organization and contribute to the functional specificity of genomic loci within the nucleus. The coupled self-assembly of the genome and nuclear landmarks is proposed as a mechanism that ensures the precise positioning of chromatin within the nucleus, leading to functional zoning rather than radial positioning. Overall, the article provides a comprehensive overview of the molecular interactions and mechanisms underlying chromatin organization, emphasizing the importance of internucleosomal interactions and the role of nuclear landmarks in shaping chromatin structure and function.