Nuclear Matrix (NuMat) is a biochemically defined entity that provides us with a snapshot of the features of the nuclear architecture. Here, we present a protocol to isolate and visualize NuMat in the intact embryo or tissues of and its applications. We remove the chromatin to reveal underlying nuclear architectural components in organismal context. This protocol couples the power of genetics with cell biological observation of the nuclear architecture. For complete details on the use and execution of this protocol, please refer to Pathak et al. (2022), Sureka et al. (2018), and Pathak et al. (2013).