The Human OCT-4 Isoforms Differ in Their Ability to Confer Self-renewal

Abstract

OCT-4 transcription factors play an important role in maintaining the pluripotent state of embryonic stem cells and may prevent expression of genes activated during differentiation. Human OCT-4 isoform mRNAs encode proteins that have identical POU DNA binding domains and C-terminal domains but differ in their N-terminal domains. We report here the cloning and characterization of the human OCT-4B isoform. Human OCT-4B cDNA encodes a 265-amino acid protein with a predicted molecular mass of 30 kDa. Embryonic stem (ES) cellbased complementation assays using ZHBTc4 ES cells showed that unlike human OCT-4A, OCT-4B cannot sustain ES cell self-renewal. In addition, OCT-4B does not bind to a probe carrying the OCT-4 consensus binding sequence, and we demonstrate that two separate regions of its N-terminal domain are responsible for inhibiting DNA binding. We also demonstrate that OCT-4B is mainly localized to the cytoplasm. Overexpression of OCT-4B did not activate transcription from OCT-4-dependent promoters, although OCT-4A did as reported previously. Furthermore, transcriptional activation by human OCT-4A was not inhibited by co-expression of OCT-4B. Taken together, these data suggest that the DNA binding, transactivation, and abilities to confer self-renewal of the human OCT-4 isoforms differ.

POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands

“…In fact, POU5F1 has been identified as an EWSR1-interacting partner [34]. In all our experiments, especially when using the NANOG promoter and POU5F1 enhancer constructs, POU5F1 wt 1 activated transcription more efficiently than POU5F1 wt 2 which is in agreement with previous findings [35]. The two POU5F1 wt variants differ in their 5´-portions, suggesting that the NH 2 -terminal domain not retained in POU5F1 wt 2 or in the chimaera may be important for transcriptional activation.…”

Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions

“…We observed slightly higher sensitivity by PCR technique than by the conventional immunohistochemistry method in detecting Oct4 expression, which is similar to other reported data (Atlasi et al, 2006;Xi et al, 2011;. This disparity could be due to the sensitivity of the technique used as PCR is observed to be more sensitive than immunohistochemsitry methods and also Oct4 is known to have two isoforms (Lee et al, 2006). Oct4 over expression had also been documented by the side population cells isolated from Lewis lung carcinoma cell line, compared to non-side population cells .…”

“…And hence, these cells are regarded as the cell of origin for tumor and also responsible for tumor relapse, metastasis and resistance to chemotherapeutic drugs (Sanada et al, 2006). Lee et al (2006) also documented that chemotherapy resistance CSCs were the factor responsible for recurrence in hepatocellular carcinomas. In-spite, the advancement in ESCC management, overall survival rate has not improved over the years.…”

Association of differential β‐catenin expression with Oct‐4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis

“…Oct-4 plays a key role in mammalian development and helps in understanding the early events in somatic differentiation of the developing 5 embryo. It was found that Oct-4 regulates the self-renewal and differentiation in embryonic stem cells [11,12], while its expression in adult stem cells with an undifferentiated phenotype helps in the maintenance of pluripotency of the population.…”

“…Oct-4 is a nuclear protein that belongs to a family of transcription factors containing the POU DNA binding domain [11]. Oct-4 plays a key role in mammalian development and helps in understanding the early events in somatic differentiation of the developing 5 embryo.…”