2013
DOI: 10.1016/j.stem.2013.05.010
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Klf4 Organizes Long-Range Chromosomal Interactions with the Oct4 Locus in Reprogramming and Pluripotency

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 durin… Show more

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Cited by 203 publications
(245 citation statements)
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References 67 publications
(94 reference statements)
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“…In agreement, the presence of macroH2A potently inhibits transcription-factor-induced reprogramming of somatic cells to pluripotency by maintaining pluripotency loci in a repressed state (Barrero et al, 2013;GasparMaia et al, 2013;Pasque et al, 2012). In addition to local chromatin structure, (Wei et al, 2013;Zhang et al, 2013).…”
Section: Three-dimensional Chromatin Architecture In Reprogrammingmentioning
confidence: 90%
See 1 more Smart Citation
“…In agreement, the presence of macroH2A potently inhibits transcription-factor-induced reprogramming of somatic cells to pluripotency by maintaining pluripotency loci in a repressed state (Barrero et al, 2013;GasparMaia et al, 2013;Pasque et al, 2012). In addition to local chromatin structure, (Wei et al, 2013;Zhang et al, 2013).…”
Section: Three-dimensional Chromatin Architecture In Reprogrammingmentioning
confidence: 90%
“…Importantly, these interactions took place specifically in those rare cells that were poised to form iPSCs, and they preceded transcriptional activation, suggesting a causal effect for 3D chromatin structure on transcription (Wei et al, 2013;Zhang et al, 2013).…”
Section: Three-dimensional Chromatin Architecture In Reprogrammingmentioning
confidence: 99%
“…87 Extending these studies of local chromosomal interactions, a genome-wide study unraveled numerous chromosomal interactions in PSCs, some of which are specific to pluripotency as shown by the loss of the interactions after differentiation of the cells. [88][89][90][91][92][93] These interactions are generally dependent on the presence of mediator, cohesin, and the CCCTC-binding factor (CTCF), which serves as an insulator dividing 2 chromosomal domains. 94 In addition, the pluripotency transcription factors Oct4, Sox2, and Klf4 mediate the chromosomal network between pluripotency genes and non-pluripotency genes.…”
Section: Long-range Chromosomal Interactionsmentioning
confidence: 99%
“…After the analysis is done, w4CSeq outputs a link navigating to the result page that has five modules: (i) summary of parameters that users have specified; (ii) summary of metrics throughout analysis; (iii) figures illustrating: (a) the genome-wide distribution of 4C regions, (b) distance distribution to reference genes, TSSs, TTSs and CpG islands of 4C sites compared to random, (c) the comparison of DNA replication timing of 4C regions versus the whole genome, and (d) the enrichment of user provided feature around 4C regions compared to random; (iv) files which users can download to perform their downstream analysis and (v) a link to the UCSC genome browser where users can visualize the contact map. Figure 1 shows the analysis of a 4C-Seq dataset (Wei et al, 2013) aimed to investigate interaction landscape centered on a distal enhancer of Oct4 gene in mouse pluripotent stem cells. Extensive interactions are observed both in cis and in trans.…”
Section: Input and Outputmentioning
confidence: 99%