Journal
STEM CELLS
Volume 30, Issue 11, Pages 2450-2459Publisher
WILEY
DOI: 10.1002/stem.1232
Keywords
Mouse ESCs; CCAAT box; NF-Y; Nanog
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Funding
- Grant Nepente from Regione Lombardia
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Totipotency of embryonic stem cells (ESCs) is controlled at the transcriptional level by a handful of transcription factors (TFs) that promote stemness and prevent differentiation. One of the most enriched DNA elements in promoters and enhancers of genes specifically active in ESCs is the CCAAT box, which is recognized by NF-Y, a trimer with histone-like subunitsNF-YB/NF-YCand the sequence-specific NF-YA. We show that the levels of the short NF-YA isoformNF-YAsis high in mouse ESCs (mESCs) and drops after differentiation; a dominant negative mutant affects expression of important stem cells genes, directly and indirectly. Protein transfections of TAT-NF-YAs stimulate growth and compensate for withdrawal of leukemia inhibitory factor (LIF) in cell cultures. Bioinformatic analysis identifies NF-Y sites as highly enriched in genomic loci of stem TFs in ESCs. Specifically, 30%50% of NANOG peaks have NF-Y sites and indeed NF-Y-binding is required for NANOG association to DNA. These data indicate that NF-Y belongs to the restricted circle of TFs that govern mESCs, and, specifically, that NF-YAs is the active isoform in these cells. STEM CELLS2012;30:24502459
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