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  • Title: Klf4 organizes long-range chromosomal interactions with the oct4 locus in reprogramming and pluripotency.
    Author: Wei Z, Gao F, Kim S, Yang H, Lyu J, An W, Wang K, Lu W.
    Journal: Cell Stem Cell; 2013 Jul 03; 13(1):36-47. PubMed ID: 23747203.
    Abstract:
    Epigenetic mechanisms underlying somatic reprogramming have been extensively studied, but little is known about the nuclear architecture of pluripotent stem cells (PSCs). Using circular chromosome conformation capture with high-throughput sequencing (4C-seq) and fluorescence in situ hybridization (FISH), we identified chromosomal regions that colocalize frequently with the Oct4 locus in PSCs. These PSC-specific long-range interactions are established prior to transcriptional activation of endogenous Oct4 during reprogramming to induced PSCs and are facilitated by Klf4-mediated recruitment of cohesin. Depletion of Klf4 leads to unloading of cohesin at the Oct4 enhancer and disrupts long-range interactions prior to loss of Oct4 transcription and subsequent PSC differentiation, suggesting a causative role for Klf4 in facilitating long-range interactions independent of its transcriptional activity. Taken together, our results delineate the basic nuclear organization at the Oct4 locus in PSCs and suggest a functional role for Klf4-mediated higher-order chromatin structure in maintaining and inducing pluripotency.
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