The tumor suppressor phosphatase and tension homolog (PTEN) is frequently mutated in human cancers, and it functions in multiple ways to safeguard cells from tumorigenesis. In the cytoplasm, PTEN antagonizes the PI3K/AKT pathway and suppresses cellular proliferation and survival. In the nucleus, PTEN is indispensable for the maintenance of genomic stability. In addition, PTEN loss leads to extensive changes in gene expression at the transcriptional level. The linker histone H1, generally considered as a transcriptional repressor, binds to the nucleosome to form a structure named the chromatosome. The dynamics between H1 and chromatin play an important role in determining gene expression. Here, we summarize the current understanding of roles of PTEN in controlling chromatin dynamics and global gene expression, which is crucial function of nuclear PTEN. We will also introduce the recent discovery of the PTEN family members and their functions.