Zfp281, also known as ZNF281, is a zinc finger transcription factor. It is involved in multiple essential biological processes such as DNA replication, pluripotent state transitions, and cell differentiation, playing a significant role in embryonic development, stem cell function, and disease-related pathways [1-7]. Genetic models, especially knockout (KO) mouse models, are crucial for studying its functions.

In KO mouse and degron knockin cell models, Zfp281 was found to directly activate Dnmt3a/3b in pluripotent stem cells, and its chromatin co-occupancy with TET1, regulated by R-loop formation, follows a “high-low-high” pattern during pluripotent state transitions, safeguarding DNA methylation and gene expression [2,5]. In mouse embryonic stem cells, Zfp281 depletion reduces PCNA levels on chromatin, impairs DNA replication, and leads to R-loop accumulation, affecting stem cell differentiation [1]. In breast cancer, down-regulation of Zfp281 in early disseminated cancer cells leads to a loss of a dormant phenotype and a switch to lung metastatic outgrowth [3]. In CD4+ T cell development, Zfp281 and Zfp148 promote the differentiation of MHC II-restricted thymocytes and cytokine expression in TH2 effector cells [4].

In summary, Zfp281 is essential for processes like DNA replication, pluripotent state transitions, cell dormancy in cancer, and T-cell development. Studies using KO mouse models have revealed its key roles in these areas, providing insights into the mechanisms of embryonic development and disease occurrence, such as cancer metastasis and immune cell differentiation [1-4, 7].