Human NANOG protein is a 305 amino acid protein with a conserved homeodomain motif that is localized to the nuclear component of cells. The homeodomain region facilitates DNA binding.
There are N-terminal, homeodomain, and C-terminal regions in human NANOG protein. Like murine NANOG, the N-terminal region of human NANOG is rich in Ser, Thr and Pro residues, and the C-terminus contains W repeats. The homeodomain in hNANOG ranges from residues 95 to 155. The conserved sequence of homeodomain are a.a. 99-100, 102, 106-107, 110, 114, 119, 121, 127-128, 132, 134, 138-140, 142-145, 147, 149, and 151-152.
NANOG is a transcription factor in embryonic stem cells (ESCs) and is thought to be a key factor in maintaining pluripotency. NANOG is thought to function in concert with other factors such as POU5F1 (Oct-4) and SOX2 to establish ESC identity. These cells offer an important area of study because of their ability to maintain pluripotency. In other words, these cells have the ability to become virtually any cell of any of the three germ layers (endoderm, ectoderm, mesoderm). It is for this reason that understanding the mechanisms that maintain a cell's pluripotency is critical for researchers to understand how stem cells work; and may lead to future advances in treating degenerative diseases.
Analysis of arrested embryos demonstrated that embryos express pluripotency marker genes such as POU5F1, NANOG and Rex1. Derived human ESC lines also expressed specific pluripotency markers:
These markers allowed for the differentiation in vitro and in vivo conditions into derivatives of all three germ layers.
POU5F1, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.
The NANOG protein has been found to be a transcriptional activator for the Rex1 promoter, playing a key role in sustaining Rex1 expression. Knockdown of NANOG in embryonic stem cells results in a reduction of Rex1 expression, while forced expression of NANOG stimulates Rex1 expression.
Besides the effects of NANOG in the embryonic stages of life, ectopic expression of NANOG in the adult stem cells can restore the proliferation and differentiation potential that is lost due to organismal aging or cellular senescence.
Humans and chimpanzees share ten NANOG pseudogenes, all in the same places: one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the poly-(A) tails characteristic of most retropseudogenes, indicating copying errors occurred during their creation. Due to the high improbability that the same pseudogenes (copying errors included) would exist in the same places in two unrelated genomes, evolutionary biologists point to NANOG and its pseudogenes as providing formidable evidence of common descent between humans and chimpanzees.
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