Yaf2, also known as YY1-associated factor 2, is a protein that plays diverse roles in various biological processes. It is involved in multiple pathways, such as those related to apoptosis, neural differentiation, and mitochondrial regulation. Yaf2 can modulate target gene transcription through epigenetic and non-epigenetic means, and its functions are of great biological importance. Genetic models, like gene knockout models, have been crucial in studying its functions [1-10].

In neural differentiation of embryonic stem cells, Yaf2 knockout promotes neural differentiation, leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on cotargeted genes, and prevents ectopic derepression of non-neuroectoderm-associated genes [1]. In zebrafish embryogenesis, depletion of zYaf2 activates apoptosis and causes developmental arrest, indicating Yaf2's role as a survival factor [4]. In human tumor cells, phosphorylated Yaf2 up-regulates FANK1 protein level by inhibiting its proteasomal degradation, and phosphorylated Yaf2 inhibits tumor cell apoptosis in a FANK1-dependent manner [2]. In aging tunicates, Yaf2 mediates the interaction between YY1 and Sirtuin6, resulting in aging-related mitochondrial downregulation [3].

In conclusion, Yaf2 has essential functions in neural differentiation, embryonic development, apoptosis regulation in tumor cells, and mitochondrial regulation during aging. Gene knockout models, especially in zebrafish and mouse embryonic stem cells, have been instrumental in revealing these functions. Understanding Yaf2's role provides insights into neural development, tumor biology, and aging-related mitochondrial changes.