Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Wang, Li; Di, Lijun; Lv, Xiang; Zheng, Wei; Xue, Zheng; Guo, Zengjun; Liu, De-Pei; Liang, Chun-Ling

doi:10.1371/journal.pone.0004629

Cited by 37 publications

(37 citation statements)

References 58 publications

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“…In mammalian nuclei, the homeobox protein SATB1 has been shown to fold chromatin into loops and regulate expression of large numbers of genes, in cell type- and cell function-specific manners[26, 38–42]. Methyl-CpG binding protein 2 (MeCP2), whose mutations cause RETT syndrome (RTT), an X-linked mental disorder[43]; MeCP2 actively forms transcriptionally-silent chromatin loop configurations at its target loci in brains of mice that are a model of RTT [24].…”

Section: Higher-order Chromatin Structuresmentioning

confidence: 99%

Genome organizing function of SATB1 in tumor progression

Kohwi‐Shigematsu

Poterlowicz

Ordinario

et al. 2013

Seminars in Cancer Biology

109

134

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When cells change functions or activities (such as during differentiation, response to extracellular stimuli, or migration), gene expression undergoes large-scale reprogramming, in cell type- and function-specific manners. Large changes in gene regulation require changes in chromatin architecture, which involve recruitment of chromatin remodeling enzymes and epigenomic modification enzymes to specific genomic loci. Transcription factors must also be accurately assembled at these loci. SATB1 is a genome organizer protein that facilitates these processes, providing a nuclear architectural platform that anchors hundreds of genes, through its interaction with specific genomic sequences; this activity allows expression of all these genes to be regulated in parallel, and enables cells to thereby alter their function. We review and describe future perspectives on SATB1 function in higher-order chromatin structure and gene regulation, and its role in metastasis of breast cancer and other tumor types.

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Section: Higher-order Chromatin Structuresmentioning

confidence: 99%

Genome organizing function of SATB1 in tumor progression

Kohwi‐Shigematsu

Poterlowicz

Ordinario

et al. 2013

Seminars in Cancer Biology

109

134

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“…For the extensively studied beta-globin locus, EKLF, FOG-1, GATA-1, GATA-2 [23;24*;25], the insulator protein CTCF [26] and the architectural protein SATB1 [27] have been shown to be involved in the loop structure. CTCF, thought to be important for loop structures, is bound across the mammalian genome at cohesin binding sites, suggesting that cohesin also has a role in the long-range structures [28–31].…”

Section: Proteins That Mediate Loopingmentioning

confidence: 99%

3D shortcuts to gene regulation

Hakim

Sung

Hager

2010

Current Opinion in Cell Biology

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Summary of recent advancesRecent technologies have allowed high resolution genome-wide binding profiles of numerous transcription factor and other proteins. A widespread observation has emerged from studies in diverse mammalian systems: most binding events are located at great distances from gene promoters. It is becoming apparent that the traditional one-dimensional view of gene regulation via the proximal cis regulatory elements is over-simplified. True proximity and functional relevance can be revealed by studying the three-dimensional structure of the genome packaged inside the nucleus. Thus the spatial architecture of the genome has attracted a lot of interest and has intensified its significance in modern cell biology. Here we discuss current methods, concepts, and controversies in this rapidly evolving field.

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“…Furthermore, SATB1 targets chromatin remodeling complexes to DNA at the base of chromatin loops, functioning as a “landing platform” for chromatin remodeling enzymes . In this way, SATB1 folds chromatin into loops and regulates the expression of a multitude of genes in cell type‐ and cell function‐specific manners . Under physiological conditions, SATB1 is required for the development of thymocytes and the activation of Th2 cells .…”

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confidence: 99%

Multiple effects of the special AT‐rich binding protein 1 (SATB1) in colon carcinoma

Frömberg

Rabe

Aigner

2014

Intl Journal of Cancer

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SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes. Overexpression has been found in various solid tumors and positively correlated with prognostic and clinicopathological properties. In colorectal cancer (CRC), SATB1 overexpression and its correlation with poor differentiation, invasive depth, TNM (tumor, nodes, metastases) stage and prognosis have been demonstrated. However, more detailed studies on the SATB1 functions in CRC are warranted. In this article, we comprehensively analyze the cellular and molecular role of SATB1 in CRC cell lines with different SATB1 expression levels by using RNAi-mediated knockdown. Using siRNAs with different knockdown efficacies, we demonstrate antiproliferative, cell cycle-inhibitory and proapoptotic effects of SATB1 knockdown in a SATB1 gene dose-dependent manner. Tumor growth inhibition is confirmed in vivo in a subcutaneous tumor xenograft mouse model using stable knockdown cells. The in-depth analysis of cellular effects reveals increased activities of caspases-3, -7, -8, -9 and other mediators of apoptotic pathways. Similarly, the analysis of E-and N-cadherin, slug, twist, b-catenin and MMP7 indicates SATB1 effects on epithelial-mesenchymal transition (EMT) and matrix breakdown. Our results also establish SATB1 effects on receptor tyrosine kinases and (proto-)oncogenes such as HER receptors and Pim-1. Taken together, this suggests a more complex molecular interplay between tumor-promoting and possible inhibitory effects in CRC by affecting multiple pathways and molecules involved in proliferation, cell cycle, EMT, invasion and cell survival.Colorectal cancer (CRC) is one of the most common causes for cancer-related deaths in the Western world. 1 Although methods of diagnosis and treatment have improved over the last few decades, the tumor stage at diagnosis is still most important for prognosis, and the overall survival of patients with advanced CRC is still poor owing to the high risk of metastasis. 2 The special AT-rich binding protein 1 (SATB1) is a global chromatin organizer that regulates the expression of a large number of genes. 3 SATB1 interacts with the altered sugarphosphate backbone of the DNA that is specific for doublestranded base-unpairing regions (BURs). BURs are often found in matrix attachment regions (MARs) at the base of chromatin loops. 4 In the nuclei of thymocytes, SATB1 has a cage-like network distribution and tethers specialized DNA sequences onto its network. 5 Furthermore, SATB1 targets chromatin remodeling complexes to DNA at the base of chromatin loops, functioning as a "landing platform" for chromatin remodeling enzymes. 6 In this way, SATB1 folds chromatin into loops and regulates the expression of a multitude of genes in cell type-and cell function-specific manners. 5,7-10 Under physiological conditions, SATB1 is required for the development of thymocytes 8 and the activation of Th2 cells. 7 Furthermore, SATB1 participates in Xchromosome inactivation, 11 development...

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Inter-MAR Association Contributes to Transcriptionally Active Looping Events in Human β-globin Gene Cluster

Cited by 37 publications

References 58 publications

Genome organizing function of SATB1 in tumor progression

Genome organizing function of SATB1 in tumor progression

3D shortcuts to gene regulation

Multiple effects of the special AT‐rich binding protein 1 (SATB1) in colon carcinoma

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