The Zuotin-related factor 1, ZRF1, has recently been identified as an epigenetic regulator of gene transcription in stem cells and cancer. During differentiation of human teratocarcinoma cells, ZRF1 promotes transcriptional induction of developmental genes that are repressed by Polycomb complexes. Importantly, ZRF1 has recently been shown to be required for both neural differentiation of embryonic stem cells (ESCs) and for maintenance of neural progenitor cell (NPC) identity. Moreover, a dual role has now emerged for ZRF1 in cancer: on the one hand, ZRF1 plays a crucial role in oncogene-induced senescence (OIS) by activating the INK4/ARF locus, thus working as a tumor suppressor; on the other hand, ZRF1 promotes leukemogenesis in acute myeloid leukemia (AML) in a Polycomb-independent fashion. Therefore, increasing evidence points to ZRF1 as a novel target for therapy of neurodegenerative diseases and cancer.
Keywords: AML, acute myeloid leukemia; ChIP, chromatin immunoprecipitation; ESC, embryonic stem cells; H2Aub1, mono-ubiquitinated histone H2A; HDAC, histone deacetylase; NPC, neural progenitor cells; OIS, oncogene-induced senescence; PRC1, polycomb repressive complex 1; PRC2, polycomb repressive complex 2; RA, retinoic acid; RARa, retinoic acid receptor a; UBD, ubiquitin binding domain; ZRF1; cancer; cell fate; development; differentiation; epigenetics; polycomb; retinoic acid; senescence; stem cell; transcription.