The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours

Abstract

During the past years, much information has been gathered regarding the genetic and epigenetic programmes leading to the specification and maintenance of primordial germ cells. Expression of the transcriptional regulator BLIMP1 (PRDM1) is regarded as the main event in germ cell specification. BLIMP1 induces a set of target genes, one of them being transcription factor TFAP2C (AP-2γ, Tcfap2c). In murine loss of function models Blimp1 and Tcfap2c share an identical phenotype, strengthening the assumption that they act in the same pathway. One major role of this pathway is the inhibition of somatic differentiation in germ cells. BLIMP1 and TFAP2C are also expressed in carcinoma in situ (CIS, IGCNU, TIN) and in seminoma. As pointed out herein, the presence of both proteins helps to explain the undifferentiated nature of these germ cell tumours. In addition, we performed a meta-analysis of high-throughput datasets searching for TFAP2C/Tcfap2c target genes. This analysis leads us to suggest Nanos3, Dmrt1 and Dnmt3b as potential TFAP2C/Tcfap2c target genes with relevance to germ cell development and germ cell tumours.