YEATS4 was first identified and isolated from glioblastoma in 1997 . The YEATS domain is a highly conserved region found in several proteins involved in chromatin modification and transcriptional regulation . YEATS4 is a nuclear protein that plays a crucial role in chromatin remodeling and epigenetic regulation .
YEATS4 is a component of the NuA4 histone acetyltransferase (HAT) complex, which is involved in the transcriptional activation of select genes by acetylating nucleosomal histones H4 and H2A . Specifically, YEATS4 recognizes and binds to acylated histone H3, with a preference for histone H3 diacetylated at lysine 18 and lysine 27 (H3K18ac and H3K27ac) or histone H3 diacetylated at lysine 14 and lysine 27 (H3K14ac and H3K27ac) . This binding facilitates the deposition of histone variant H2AZ1/H2A.Z into specific chromatin regions, promoting the transcription of actively transcribed genes .
YEATS4 has been implicated in the development and progression of various cancers. It is amplified and overexpressed in several malignancies, including astrocytomas, uterine fibroids, liposarcoma, breast cancer, liver cancer, pancreatic cancer, gastric cancer, non-small cell lung cancer, colorectal cancer, and ovarian cancer . The upregulation of YEATS4 promotes DNA damage repair and prevents cell death, while its downregulation inhibits DNA replication and induces apoptosis . Aberrant activation of YEATS4 is associated with changes in drug resistance, epithelial-mesenchymal transition, and the migration and invasion capacity of tumor cells .
Given its role in cancer progression, YEATS4 has emerged as a potential target for cancer therapy. Specific inhibition of YEATS4 expression or activity may be an effective strategy for inhibiting the proliferation, motility, differentiation, and survival of tumor cells . Research is ongoing to develop small-molecule inhibitors that target YEATS4 and to further understand its biological functions, metabolism, and regulatory mechanisms in various cancers .