Oct4 links multiple epigenetic pathways to the pluripotency network

Abstract

Oct4 is a well-known transcription factor that plays fundamental roles in stem cell self-renewal, pluripotency, and somatic cell reprogramming. However, limited information is available on Oct4-associated protein complexes and their intrinsic protein-protein interactions that dictate Oct4’s critical regulatory activities. Here we employed an improved affinity purification approach combined with mass spectrometry to purify Oct4 protein complexes in mouse embryonic stem cells (mESCs), and discovered many novel Oct4 partners important for self-renewal and pluripotency of mESCs. Notably, we found that Oct4 is associated with multiple chromatin modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming. Our study establishes a solid biochemical basis for genetic and epigenetic regulation of stem cell pluripotency and provides a framework for exploring alternative factor-based reprogramming strategies.

The transcriptional regulation of pluripotency

“…Through the coupling of affinity purification methods with mass spectrometry technology, numerous co-binding proteins of the core pluripotency transcription factors have been identified [33][34][35][36][37][38][39][40]. Taken together, these studies reveal an extensive protein-protein interaction network which includes other ESC transcription regulators, chromatin remodeling and modifying factors, DNA methyltransferases and Polycomb group proteins (PcG).…”

Ten-Eleven Translocation 1 (Tet1) Is Regulated by O-Linked N-Acetylglucosamine Transferase (Ogt) for Target Gene Repression in Mouse Embryonic Stem Cells

“…Ogt is essential for mouse early development (24). Ogt can also interact with and modify ES cell pluripotency factors such as Oct4, Sox2, and Zfp281 (25)(26)(27)(28)(29)(30). To further confirm the interaction between Ogt and Tet1, we carried out co-IP experiments.…”

The 2013 special issue on stem cell biology

“…Along the way, the field of stem cell biology has naturally become an important research area covered by papers published in Cell Research [2]. For instance, in the past year of 2012, Cell Research has published a number of important papers related to the stem cell field, covering diverse aspects and topics such as induced pluripotent stem (iPS) cells [3][4][5][6][7], mechanistic studies of pluripotency and differentiation [8][9][10][11], modeling of human diseases using stem cell-based systems [6,12], direct reprogramming of somatic cells to other cell types without passing through an pluripotent intermediate [13][14][15][16], as well as neural crest stem cells [17] and cancer stem cells [18][19][20].…”