Chromatin regulation: How complex does it get?

Meier, Karin; Brehm, Alexander

doi:10.4161/15592294.2014.971580

Cited by 100 publications

(75 citation statements)

References 102 publications

(138 reference statements)

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“…Gene expression is tightly regulated at multiple levels to ensure appropriate transcriptomes; the chromatin state is a major determinant of transcription (55). Our findings are consistent with a model wherein Cdx members impact the chromatin state and target gene expression through recruitment of Brg1 and associated SWI-SNF-dependent chromatin remodeling (Fig.…”

Section: Journal Of Biological Chemistry 3393supporting

confidence: 78%

Cdx2 Regulates Gene Expression through Recruitment of Brg1-associated Switch-Sucrose Non-fermentable (SWI-SNF) Chromatin Remodeling Activity

Nguyen

Savory

Brooke-Bisschop

et al. 2017

Journal of Biological Chemistry

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Edited by John M. DenuThe packaging of genomic DNA into nucleosomes creates a barrier to transcription that can be relieved through ATP-dependent chromatin remodeling via complexes such as the switch-sucrose non-fermentable (SWI-SNF) chromatin remodeling complex. The SWI-SNF complex remodels chromatin via conformational or positional changes of nucleosomes, thereby altering the access of transcriptional machinery to target genes. The SWI-SNF complex has limited ability to bind to sequencespecific elements, and, therefore, its recruitment to target loci is believed to require interaction with DNA-associated transcription factors. The Cdx family of homeodomain transcript ion factors (Cdx1, Cdx2, and Cdx4) are essential for a number of developmental programs in the mouse. Cdx1 and Cdx2 also regulate intestinal homeostasis throughout life. Although a number of Cdx target genes have been identified, the basis by which Cdx members impact their transcription is poorly understood. We have found that Cdx members interact with the SWI-SNF complex and make direct contact with Brg1, a catalytic member of SWI-SNF. Both Cdx2 and Brg1 co-occupy a number of Cdx target genes, and both factors are necessary for transcriptional regulation of such targets. Finally, Cdx2 and Brg1 occupancy occurs coincident with chromatin remodeling at some of these loci. Taken together, our findings suggest that Cdx transcription factors regulate target gene expression, in part, through recruitment of Brg1-associated SWI-SNF chromatin remodeling activity.The Cdx genes are vertebrate orthologs of Drosophila caudal and encode homeodomain transcriptional factors. In the mouse, the three members of this family (Cdx1, Cdx2, and Cdx4) are co-expressed in the caudal embryo in all three germ layers commencing at mid-gastrulation and play overlapping roles in a number of developmental programs, including axial elongation, endoderm specification, and anterior-posterior vertebral patterning (1-6). Both Cdx1 and Cdx2 are also expressed in the intestinal epithelium throughout life, where they play critical roles in intestinal homeostasis (7-11) and can function as tumor suppressors (12-15). Although Cdx members play critical roles in governing gene expression during development and in the adult intestine, little is known about the mechanisms by which Cdx members regulate target gene transcription.The packaging of DNA into nucleosomes creates a barrier to transcription by obstructing access of the basal transcription machinery as well as modulating access of other transcriptional regulators to their DNA binding motifs (16 -19). Alteration of the chromatin structure by ATP-dependent remodeling complexes can alleviate these constraints, and such complexes play important roles in the transcriptional regulation of many eukaryotic genes. Such complexes include the switch-sucrose non-fermentable (SWI-SNF) 2 chromatin-remodeling complex (16, 20 -22), which remodels the chromatin structure via conformational or positional changes of nucleosomes (23,24). Because the SWI-...

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Section: Journal Of Biological Chemistry 3393supporting

confidence: 78%

Cdx2 Regulates Gene Expression through Recruitment of Brg1-associated Switch-Sucrose Non-fermentable (SWI-SNF) Chromatin Remodeling Activity

Nguyen

Savory

Brooke-Bisschop

et al. 2017

Journal of Biological Chemistry

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“…6 PICH belongs to a sub-class of SNF2 proteins related to the RAD54 protein, which is involved in homologous recombination. 7 In addition to a canonical SNF2-like ATPase domain, PICH contains a so-called PICH family domain of unknown function.…”

Section: Introductionmentioning

confidence: 99%

PICH promotes mitotic chromosome segregation: Identification of a novel role in rDNA disjunction

Nielsen

Hickson

2016

Cell Cycle

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PICH is an SNF2-family DNA translocase that appears to play a role specifically in mitosis. Characterization of PICH in human cells led to the initial discovery of "ultra-fine DNA bridges" (UFBs) that connect the 2 segregating DNA masses in the anaphase of mitosis. These bridge structures, which arise from specific regions of the genome, are a normal feature of anaphase but had escaped detection previously because they do not stain with commonly used DNA dyes. Nevertheless, UFBs are important for genome maintenance because defects in UFB resolution can lead to cytokinesis failure. We reported recently that PICH stimulates the unlinking (decatenation) of entangled DNA by Topoisomerase IIa (Topo IIa), and is important for the resolution of UFBs. We also demonstrated that PICH and Topo IIa co-localize at the rDNA (rDNA). In this Extra View article, we discuss the mitotic roles of PICH and explore further the role of PICH in the timely segregation of the rDNA locus.

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“…Modulation of transcription of oncogenes or tumor-suppressor genes is an oncology-related function of lncRNAs (25). Posttranscriptional functions of lncRNAs can trigger alternative splicing by pairing with other RNAs (16,26).…”

Section: Long νOn-coding Rna (Lncrna) -General Featuresmentioning

confidence: 99%

“…PRC1 is a multiprotein complex composed of proteins such as BMI1, RING1, RING2 and chromobox proteins (CBX) and is able to ubiquitinylate histone H2A at lysine 119 (26,27). PRC2 is assembled by EED, SUZ12 and histone methyltransferase EZH2 which trimethylates histone 3 lysine 27 (26,27).…”

Section: Long νOn-coding Rna (Lncrna) -General Featuresmentioning

confidence: 99%

Long Non-coding RNAs and their Role in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

124

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Abstract.Metastasis is the major cause of death in patients with cancer. It is mediated by a multi-step process referred to as the metastatic cascade (1, 2). Initial steps include local invasion and migration, angiogenesis, epithelialmesenchymal transition (EMT) and intravasation. Tumor cells enter the circulation as single cells or circulating tumor cell clusters, are coated by platelets to escape an immune response and subsequently arrest in capillaries in distant organs as a prerequisite for extravasation. Colonization starts by homing of tumor cells in supporting niches of the organ parenchyma, followed by a latency phase which can last from several months to decades. A prerequiste for overt outgrowth of micrometastases is their adaptation to the local microenvironment and acquisition of colonisation-promoting traits (3-6). The pattern of colonized distant organs depends on the tumor type and can range from predominant spread to one organ and colonization of different types of organs sequentially or simultaneously (7). Several genes and their products have been identified to mediate crucial steps of the metastatic process such as metastasis initiation and progression, as well as organ-specific functions of metastasis (virulence) (8, 9). These gene products include proteases, chemokines, cytokines and their receptors, angiogenic factors, intracellular and transmembrane kinases, adhesion molecules, components of the extracellular matrix (ECM), GPI-linked receptors and carbohydrate metabolism-related enzymes (8, 9). More recently, an important impact of RNA-related molecules for metastasis has emerged. MicroRNAs (miRs) and other types of RNA modulate metastasis via regulatory networks (10,11). In this review we focus on the role of long non-coding RNAs (lncRNA) as promoters or inhibitors of metastasis in different tumor entities since there is an urgent need to define new targets for therapeutic intervention. With the exception of denosumab for treatment of bone metastases, all other agents evaluated in clinical studies for treatment of metastatic disease gave rise to mixed or disappointing results (6).

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Chromatin regulation: How complex does it get?

Cited by 100 publications

References 102 publications

Cdx2 Regulates Gene Expression through Recruitment of Brg1-associated Switch-Sucrose Non-fermentable (SWI-SNF) Chromatin Remodeling Activity

Cdx2 Regulates Gene Expression through Recruitment of Brg1-associated Switch-Sucrose Non-fermentable (SWI-SNF) Chromatin Remodeling Activity

PICH promotes mitotic chromosome segregation: Identification of a novel role in rDNA disjunction

Long Non-coding RNAs and their Role in Metastasis

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