Insulators Target Active Genes to Transcription Factories and Polycomb-Repressed Genes to Polycomb Bodies

Li, Hua Bing; Ohno, Katsuhito; Gui, Hongxing; Pirrotta, Vincenzo

doi:10.1371/journal.pgen.1003436

Cited by 64 publications

(63 citation statements)

References 47 publications

(80 reference statements)

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“…This is consistent with numerous studies linking transcriptional co-regulation to spatial clustering of the relevant genes and their cis-regulatory elements [26][27][28][29][30][31][32] around the nucleoplasmic supra-molecular entities that harbor most nuclear transcription-around transcription factories [19].…”

Section: Large-scale Reorganization Of Higher-order Chromatin Structusupporting

confidence: 92%

Contribution of 3D Chromatin Architecture to the Maintenance of Pluripotency

Brant

Papantonis

2015

Curr Stem Cell Rep

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Maintenance of pluripotency, lineage commitment and differentiation of mammalian embryonic stem cells into all somatic cell types involves differential regulation of different subsets of genes, as does reprogramming of somatic cells back into a pluripotent state. It is now understood that the three-dimensional organization of the human genome asserts a key role in these processes in two ways. First, by providing a largely invariable scaffold onto which dynamic changes in chromatin may manifest; second, by allowing the spatial clustering of genes contributing to the same functional pathways. In this review, we discuss the rapidly growing volume of literature on the structure-to-function relationship of mammalian genomes as regards key developmental transitions of stem cell populations.

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Section: Large-scale Reorganization Of Higher-order Chromatin Structusupporting

confidence: 92%

Contribution of 3D Chromatin Architecture to the Maintenance of Pluripotency

Brant

Papantonis

2015

Curr Stem Cell Rep

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“…Does CTCF impart specificity to MLL1-binding at the intergenic CGIs? Several reports in Drosophila have implicated CTCF in mediating the repressive properties of PREs by enabling long-range PRE-PRE interactions (Li et al, 2011; Li et al, 2013). …”

Section: Discussionmentioning

confidence: 99%

An Evolutionary Conserved Epigenetic Mark of Polycomb Response Elements Implemented by Trx/MLL/COMPASS

Rickels

Collings

et al. 2016

Molecular Cell

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Polycomb Response Elements (PREs) are specific DNA sequences that stably maintain the developmental pattern of gene expression. Drosophila PREs are well characterized, whereas the existence of PREs in mammals remains debated. Accumulating evidence supports a model in which CGIs recruit Polycomb-Group complexes (PcG), however, which subset of CGIs are selected to serve as PREs is unclear. Trithorax (Trx) positively regulates gene expression in Drosophila and co-occupies PREs to antagonize Polycomb-dependent silencing. Here, we demonstrate that Trx-dependent H3K4 dimethylation (H3K4me2) marks Drosophila PREs and maintains the developmental expression pattern of nearby genes. Similarly, the mammalian Trx homology, MLL1, deposits H3K4me2 at CpG dense regions that could serve as PREs. In the absence of MLL1 and H3K4me2, H3K27me3 levels, a mark of Polycomb Repressive Complex 2 (PRC2), increase at these loci. By inhibiting PRC2-dependent H3K27me3 in the absence of MLL1, we can rescue expression of these loci, demonstrating a functional balance between MLL1 and PRC2 activities at these sites. Thus, our study provides rules for identifying cell-type specific functional mammalian PREs within the human genome.

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“…CTCF has previously been shown to control the chromatin architecture and expression of genes in the major histocompatibility complex class II and interferon-γ loci, as well as V(D)J recombination (39, 40, 65, 66). Regulation of gene expression by CTCF is thought to be due to the formation of long-range interactions that bring enhancers and promoters together (36, 39, 67). Here, two CTCF sites flank the Pdcd1 gene and likely serve to isolate it from its neighboring genes.…”

Section: Discussionmentioning

confidence: 99%

STAT3, STAT4, NFATc1, and CTCF Regulate PD-1 through Multiple Novel Regulatory Regions in Murine T Cells

Austin

Majumder

et al. 2014

The Journal of Immunology

142

125

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Programmed cell death-1 (PD-1) is a crucial negative regulator of CD8 T cell development and function, yet the mechanisms that control its expression are not fully understood. Through a non-biased DNase I hypersensitivity assay, four novel regulatory regions within the Pdcd1 locus were identified. Two of these elements flank the locus, bind the transcriptional insulator protein CTCF, and interacted with each other, creating a potential regulatory compartmentalization of the locus. In response to T cell activation signaling, NFATc1 bound to two of the novel regions that function as independent regulatory elements. STAT binding sites were identified in these elements as well. In splenic CD8 T cells, TCR-induced PD-1 expression was augmented by interleukin 6 and 12, inducers of STAT3 and STAT4 activity, respectively. IL-6 or IL-12 on its own did not induce PD-1. Importantly, STAT3/4 and distinct chromatin modifications were associated with the novel regulatory regions following cytokine stimulation. The NFATc1/STAT regulatory regions were found to interact with the promoter region of the Pdcd1 gene providing a mechanism for their action. Together these data add multiple novel distal regulatory regions and pathways to the control of PD-1 expression and provide a molecular mechanism by which proinflammatory cytokines, such as IL-6 or IL-12 can augment PD-1 expression.

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Insulators Target Active Genes to Transcription Factories and Polycomb-Repressed Genes to Polycomb Bodies

Cited by 64 publications

References 47 publications

Contribution of 3D Chromatin Architecture to the Maintenance of Pluripotency

Contribution of 3D Chromatin Architecture to the Maintenance of Pluripotency

An Evolutionary Conserved Epigenetic Mark of Polycomb Response Elements Implemented by Trx/MLL/COMPASS

STAT3, STAT4, NFATc1, and CTCF Regulate PD-1 through Multiple Novel Regulatory Regions in Murine T Cells

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