Chromosomes were first discovered by Karl Wilhelm von Nägeli in 1842 and were thus named “chromosomes” by Heinrich Wilhelm Gottfried von Waldeyer-Hartz in 1888. Chromosomes are now understood to be “super molecules” consisting of DNA

proteins, and appearing at the M phase in mitosis and meiosis. The chromosomal higher-order structure is established during the M phase and is completed at the metaphase stage (see Chapter 9). The overall higher-order structure of chromosomes remains an enigma in spite of the efforts of numerous researchers, and dozens of different models have been presented. One of the main obstacles in characterizing the chromosomal higher-order structure model lies in the fact that the chromosome constituent proteins have not fully been identified or analyzed, although it is well known that each chromosome contains two DNA molecules, five major histone proteins, and nonhistone proteins. In this chapter, we describe a human metaphase chromosome protein framework, defined using the results of proteome analysis of human metaphase chromosomes. We present a “four-layer model” of human metaphase chromosomes-the first chromosome structural model based on information of the chromosomal constituent proteins and their localization.