Oct-4: More than a Pluripotent Marker?

Oct-4/ Pou5f1/ Oct-3, a POU domain family protein acts as a crucial transcription factor during embryonic development. It helps in maintenance of self renewal as well as pluripotential state of embryonic stem (ES) cells. Its expression starts right from 2 cell stage especially prior to 8 cell stage till the blastocyst stage where it is strongly expressed in inner cell mass (ICM). Thereafter, it is located predominantly in primordial germ cells (PGCs) till the birth. It targets particularly those genes which bear an octameric motif ATGCAAAT in promoter or enhancer region. Most of the target genes of Oct-4 are expressed in undifferentiated ES cells and knockdown of Oct-4 results in ES cell differentiation as a result of down regulation of targets of Oct-4 which are expressed in ES cells. Since, Oct-4 is crucial for embryo survival its expression needs tight regulation. Oct-4 is carefully regulated epigenetically as well as by several other factors. DNA methylation and histone modification play an important role in expression of Oct-4 while proximal promoter, enhancer and distal enhancer are the crucial regulatory elements present on Oct-4 upstream region. There is increasing evidence that Oct-4 is expressed in adult stem cells and these stem cells can get converted to cancer stem cells. Since, it is expressed in germ cells, immunohistochemical localization of Oct-4 and thereby its role as a marker for germ cell tumor detection is increasing. Thus, role of Oct-4 is not only restricted as a marker for undifferentiated cells; it is also proving to be crucial factor which targets several genes involved in ES cell survival as well as help in establishing germ cell origin of metastatic tumors.