Estrogen fueled, nuclear Kiss

Belmont, Andrew S.

doi:10.4161/nucl.1.5.13051

Cited by 8 publications

(5 citation statements)

References 16 publications

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“…These findings are in contrast to the observation that liganded estrogen receptors rapidly induce specific interchromosomal contacts between target genes (Hu et al 2008) but in agreement with other reports showing that activation of these genes does not affect their positioning (Kocanova et al 2010). The discrepancy could arise from the different culture conditions or source cells (Belmont 2010). The moderate changes in the spatial environments of our GR-regulated loci are in agreement with a previous finding that chromatin has constrained mobility, limited to a range of ;0.5 mm, in mammalian cells (Chubb et al 2002).…”

Section: Discussionsupporting

confidence: 88%

Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements

Hakim¹,

Sung²,

Voss³

et al. 2011

Genome Res.

139

137

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The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study, we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture on chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses colocalize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNase I-hypersensitive sites that comprehensively mark cell-type -specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and this organization is significantly correlated with cell-type-specific chromatin sites accessible to regulatory factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general and to permit efficient gene regulation.

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Section: Discussionsupporting

confidence: 88%

Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements

Hakim¹,

Sung²,

Voss³

et al. 2011

Genome Res.

139

137

View full text Add to dashboard Cite

show abstract

“…Moreover, while the initial study suggested a diploid representation of chromosomes 21 and 2 which harbor the TFF1 and GREB1 genes respectively [85], the MCF7 cells used in this study are from hypertriploid to hypotetraploid with 4-6 TFF1 or GREB1 gene loci [93]. Thus, further investigation is required to resolve this discrepancy [94]. …”

Section: Nuclear Bodies Exert Diverse and Important Biological Functionsmentioning

confidence: 99%

Biogenesis and function of nuclear bodies

2011

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Nuclear bodies including nucleoli, Cajal bodies, nuclear speckles, Polycomb bodies, and paraspeckles are membrane-less subnuclear organelles. They are steady-state structures that dynamically respond to basic physiological processes as well as various forms of stress, altered metabolic conditions and alterations in cellular signaling. The formation of specific nuclear bodies has been suggested to follow stochastic and ordered assembly models. In addition, a seeding mechanism has been proposed to assemble, maintain, and regulate particular nuclear bodies. In coordination with noncoding RNAs, chromatin modifiers and other machineries, various nuclear bodies have been shown to sequester and modify proteins, process RNAs and assemble ribonucleoprotein complexes, as well as epigenetically regulate gene expression. Understanding the functional relationships between the three-dimensional organization of the genome and nuclear bodies is essential to fully uncover the regulation of gene expression and its implications in human diseases.

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“…Another study suggested that long distance interchromosomal interactions are actively created after ER stimulation (Hu et al, 2008); however these studies failed to be reproduced by others (Kocanova et al, 2010). The near term resolution of this controversy is important to the field (Belmont, 2010). …”

Section: Impact Of Chromatin 3d Structurementioning

confidence: 99%

Impact of chromatin structure on PR signaling: Transition from local to global analysis

Grøntved

Hager

2012

Molecular and Cellular Endocrinology

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The progesterone receptor (PR) interacts with chromatin in a highly dynamic manner that requires ongoing chromatin remodeling, interaction with chaparones and activity of the proteasome. Here we discuss dynamic interaction of steroid receptor with chromatin, with special attention not only to PR but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS-seq) show that a large fraction of receptor binding events occur at pre-accessible chromatin. Thus factors which generate and maintain accessible chromatin during development, and in fully differentiated tissue, contribute a major fraction of receptor tissue specificity. In addition, chromosome conformation capture techniques suggest that steroid receptors preferentially sequester within distinct nuclear hubs. We will integrate dynamic studies from single cells and genomic studies from cell populations, and discuss how genomic approaches have reshaped our current understanding of mechanisms that control steroid receptor interaction with chromatin.

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Estrogen fueled, nuclear Kiss

Cited by 8 publications

References 16 publications

Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements

Diverse gene reprogramming events occur in the same spatial clusters of distal regulatory elements

Biogenesis and function of nuclear bodies

Impact of chromatin structure on PR signaling: Transition from local to global analysis

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