Skip to main content

Table 3 Dysregulation of transcriptional networks in stem cells and disease

From: Transcriptomic analysis of pluripotent stem cells: insights into health and disease

Gene/protein Role in ESCs Role in disease
c-MYC Involved in the expression of self-renewal genes [101]; recruits p-TEFb to initiate transcriptional pause release of RNA polymerase II [29] Most common gene duplication in cancer [73]; c-Myc appears to be responsible for the gene expression signature of cancer cells [9]
LIN28 Maintains ESC pluripotency by binding and inhibiting the maturation of pro-differentiation let-7 miRNA; LIN28 is also a hiPSC reprogramming factor [74] Highly expressed in poorly differentiated and low prognosis tumors; as let-7 silences the expression of oncogenes c-Myc, K-Ras, Hmga2 and the gene encoding cyclin-D1, Lin28 suppression of let-7 miRNA may thus promote oncogenesis [74]
SOX2 A core ESC transcription factor together with Oct4 and Nanog. Regulates the expression of pluripotency genes, and suppresses lineage-specific genes [23, 24]; Sox2 is also an iPSC reprogramming factor [4] Mutation in SOX2 causes anophthalmia (congenital loss of eyeballs) in humans. Proposed to cooperate with CHD7 to regulate genes involved in Alagille, Pallister-Hall and Feingold syndromes [76]
CHD7 Binds with core ESC factors and p300 at gene enhancers to modulate ESC-specific gene expression [77] Mutations in CHD7 result in CHARGE syndrome; proposed to cooperate with SOX2 to regulate genes involved in Alagille, Pallister-Hall and Feingold syndromes [76]
Mediator Physically links the Oct4/Sox2/Nanog-bound gene enhancers to active gene promoters via chromatin looping [29]; necessary for normal gene activity Mutations in Mediator are associated with Opitz-Kaveggia, Lujan, and transposition of the great arteries syndromes; also implicated in schizophrenia, colon cancer progression [1] and uterine leiomyomas [102]
Cohesin Proposed to bind and stabilize the Oct4/Sox2/Nanog enhancer-promoter chromatin loops [1]; necessary for normal gene activity Cohesin mutations implicated in Cornelia de Lange syndrome, whereby patients exhibit developmental defects and mental retardation due to dysregulation of gene expression [29]
Nipbl Binds with mediator complex to allow loading of cohesion and formation of stable chromatin loop [29] Nipbl mutations implicated in Cornelia de Lange syndrome, whereby patients exhibit developmental defects and mental retardation due to dysregulation of gene expression [29]
  1. ESC, embryonic stem cell; hiPSC, human induced pluripotent stem cell; iPSC, induced pluripotent stem cell; miRNA, microRNA.