3D shortcuts to gene regulation

Hakim, Ofir; Sung, Myong-Hee; Hager, Gordon L.

doi:10.1016/j.ceb.2010.04.005

Cited by 33 publications

(22 citation statements)

References 80 publications

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“…STAT proteins, like many transcription factors, bind to numerous intergenic regions at considerable distances from any known gene . The marked spatial clustering of STAT4 binding sites in Th1 cells supports a high local concentration of STAT4 proteins within a close 3D neighborhood of Ifng in the nucleus, potentially facilitating transcriptional regulation (Hakim et al 2010Wang et al 2011). Recent reports have implicated the presence of regulatory elements, observed as DNase I hypersensitive sites (DHSs), as the most prominent genomic feature within physical DNA interaction regions (Lieberman-Aiden et al 2009;Hakim et al 2011;Yaffe and Tanay 2011).…”

Section: Discussionmentioning

confidence: 99%

“…These transcription factors modify the gene expression program to direct the proper course of differentiation and enforce the lineage-specific function. Notably, accumulating studies document abundance of nongenic binding sites for most transcription factors, suggesting that the spatial encounters between genomic loci are important for their genomewide effects (Biddie et al 2010;Hakim et al 2010;Wei et al 2010;John et al 2011).…”

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confidence: 99%

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Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation

et al. 2012

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Higher-order genome organization shows tissue-specific patterns. However, functional relevance and the mechanisms shaping the genome architecture are poorly understood. Here we report a profound shift from promiscuous to highly selective genome organization that accompanies the effector lineage choice of differentiating T cells. As multipotent naive cells receive antigenic signals and commit to a T helper (Th) pathway, the genome-wide contacts of a lineage-specific cytokine locus are preferentially enriched for functionally relevant genes. Despite the establishment of divergent interactomes and global reprogramming of transcription in Th1 versus Th2, the overall expression status of the contact genes is surprisingly similar between the two lineages. Importantly, during differentiation, the genomic contacts are retained and strengthened precisely at DNA binding sites of the specific lineage-determining STAT transcription factor. In cells from the specific STAT knock-out mouse, the signature cytokine locus is unable to shed the promiscuous contacts established in the naive T cells, indicating the importance of genomic STAT binding. Altogether, the global aggregation of STAT binding loci from genic and nongenic regions highlights a new role for differentiation-promoting transcription factors in direct specification of higher-order nuclear architecture through interacting with regulatory regions. Such subnuclear environments have significant implications for efficient functioning of the mature effector lymphocytes.

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Section: Discussionmentioning

confidence: 99%

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Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation

et al. 2012

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“…Likely, there is no direct interaction between genomic regions around ϩ73kb and ϩ578 bp, as we did not detect any ligated PCR product with respective primers. Nonetheless, such spatial arrangements could still play a role in transcription regulation (12,31). There is no available restriction site that allows us to study genomic regions closer to TSS than ϩ578 region.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes

Kuo

Liu

Chen

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Glucocorticoids and FoxO3 exert similar metabolic effects in skeletal muscle. FoxO3 gene expression was increased by dexamethasone (Dex), a synthetic glucocorticoid, both in vitro and in vivo. In C2C12 myotubes the increased expression is due to, at least in part, the elevated rate of FoxO3 gene transcription. In the mouse FoxO3 gene, we identified three glucocorticoid receptor (GR) binding regions (GBRs): one being upstream of the transcription start site, −17kbGBR; and two in introns, +45kbGBR and +71kbGBR. Together, these three GBRs contain four 15-bp glucocorticoid response elements (GREs). Micrococcal nuclease (MNase) assay revealed that Dex treatment increased the sensitivity to MNase in the GRE of +45kbGBR and +71kbGBR upon 30- and 60-min Dex treatment, respectively. Conversely, Dex treatment did not affect the chromatin structure near the −17kbGBR, in which the GRE is located in the linker region. Dex treatment also increased histone H3 and/or H4 acetylation in genomic regions near all three GBRs. Moreover, using chromatin conformation capture (3C) assay, we showed that Dex treatment increased the interaction between the −17kbGBR and two genomic regions: one located around +500 bp and the other around +73 kb. Finally, the transcriptional coregulator p300 was recruited to all three GBRs upon Dex treatment. The reduction of p300 expression decreased FoxO3 gene expression and Dex-stimulated interaction between distinct genomic regions of FoxO3 gene identified by 3C. Overall, our results demonstrate that glucocorticoids activated FoxO3 gene transcription through multiple GREs by chromatin structural change and DNA looping.

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“…Among various other reasons, osmotic inhibition and the toxicity of salt ions are considered to be the main reasons of salinity (Hakim et al, 2010). A detailed study on seed germination, seedling growth and other growth attributes under saline conditions suggested that germination, shoot and root length, tiller number, leaf area index and grain yield were decreased when exposed to high saline conditions (150 mM) in almost all varieties studied (Ashraf et al, 1991;Khan et al, 1995;Hasanuzzaman et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

GA Mediated OsZAT-12 Expression Improves Salt Resistance of Rice

Imran¹,

Kamran²,

Shafiq‐ur‐Rehman³

et al. 2016

IJAB

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Abiotic stress prevents plants from absorbing available nutrients resulting in yield loss and soil contamination. Growth regulators like gibberellic acid (GA) may improve plant growth under stress conditions. This study was conducted to evaluate the role of GA on the rice performance under saline conditions and to investigate its effects on regulatory gene expression by GA-mediated seed priming. Seeds of rice variety KSK 282 were primed in GA solution (0, 50, 100 and 150 ppm) and grown under different salt (NaCl) concentrations (0, 50, 100 and 150 mM). Increase in salt concentration led to decrease in rice growth. GA priming reversed the negative effects of salt stress and enhanced different growth attributes like germination, seedling growth and weight, while decreased the concentration of toxic ions such as Na + in some treatments. However, GA priming was not very effective on Chlorophyll a, b (Chl-a, Chl-b) and total carotene contents. Reverse transcription polymerase chain reaction (RT-PCR) approach was used to study the effect of GA-mediated seed priming on the expression of two stress responsive genes, OsZat 12-1 (LOC_Os01g62130 also called ZOS1-14 -C2H2 zinc finger protein) and OsZat 12-9 (LOC_Os01g62190 also called ZOS1-15 -C2H2 zinc finger protein). There was no or very low expression of OsZat 12-1 and OsZat 12-9 in hydroprimed seeds under all salt stress conditions tested, while induction of gene expression was observed for plants raised from GA primed seeds under salt stress. In conclusion, GA regulated the growth at early stages of rice life cycle by inducing regulatory genes expression; therefore it is noteworthy that while studying salinity factor, the induction of genetic determinants (genes) by plant growth regulators should also be considered.

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3D shortcuts to gene regulation

Cited by 33 publications

References 80 publications

Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation

Spatial congregation of STAT binding directs selective nuclear architecture during T-cell functional differentiation

Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes

GA Mediated OsZAT-12 Expression Improves Salt Resistance of Rice

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