Psip1-flox Mouse

Psip1, also known as LEDGF (Lens epithelium-derived growth factor), is a chromatin protein. It has histone chaperone activity and is associated with the transcriptional elongation complex. It plays a role in recruiting RNA processing and DNA repair factors to transcription sites, thus maintaining genome integrity. It is also involved in pathways related to cell-cycle regulation, alternative splicing, and may have a connection with arginine metabolism in T-cells [1,3,4,5].

In gene-knockout (KO) studies, depletion of Psip1 in human and mouse cell lines led to an accumulation of R-loops and DNA damage at gene promoters, causing local transcriptional arrest and transcription-replication conflict [1]. In a mouse model of T-cell acute lymphoblastic leukemia (T-ALL), loss of Psip1 accelerated T-ALL initiation, which was correlated with reduced H3K27me3 binding. However, in T-ALL cell lines, its loss impaired cell proliferation [2]. In breast cancer, depletion of Psip1 in TNBC cell lines reduced tumorigenicity and metastatic properties [4].

In conclusion, Psip1 is crucial for maintaining genome integrity at transcription sites, and it plays a dual role in T-ALL, either as a tumor suppressor during initiation or a dependency factor in maintenance. In breast cancer, it promotes tumorigenicity by regulating cell-cycle genes. The KO and other loss-of-function experiments in mouse models have significantly enhanced our understanding of Psip1's role in these disease conditions.