Lsh Mediated RNA Polymerase II Stalling at HoxC6 and HoxC8 Involves DNA Methylation

Tao, Yongguang; Xi, Sichuan; Briones, Victorino; Muegge, Kathrin

doi:10.1371/journal.pone.0009163

Cited by 42 publications

(50 citation statements)

References 59 publications

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“…The assay was performed as described previously (68). Briefly, after lysis of single-cell suspensions, chromatin was digested with MNase (Thermo Scientific); DNA was extracted by phenol:chloroform and separated on a 1.5% agarose gel.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis

Xu²,

Shan³

et al. 2013

J. Clin. Invest.

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125

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MicroRNAs are critical mediators of stem cell pluripotency, differentiation, and malignancy. Limited information exists regarding microRNA alterations that facilitate initiation and progression of human lung cancers. In this study, array techniques were used to evaluate microRNA expression in normal human respiratory epithelia and lung cancer cells cultured in the presence or absence of cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly repressed miR-487b. Subsequent experiments demonstrated that miR-487b directly targeted SUZ12, BMI1, WNT5A, MYC, and KRAS. Repression of miR-487b correlated with overexpression of these targets in primary lung cancers and coincided with DNA methylation, de novo nucleosome occupancy, and decreased H2AZ and TCF1 levels within the miR-487b genomic locus. Deoxyazacytidine derepressed miR-487b and attenuated CSC-mediated silencing of miR-487b. Constitutive expression of miR-487b abrogated Wnt signaling, inhibited in vitro proliferation and invasion of lung cancer cells mediated by CSC or overexpression of miR-487b targets, and decreased growth and metastatic potential of lung cancer cells in vivo. Collectively, these findings indicate that miR-487b is a tumor suppressor microRNA silenced by epigenetic mechanisms during tobacco-induced pulmonary carcinogenesis and suggest that DNA demethylating agents may be useful for activating miR-487b for lung cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis

Xu²,

Shan³

et al. 2013

J. Clin. Invest.

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125

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“…66,67 A de novo chromosome 5q21.1 deletion that disrupts the CHD1 was found in a female with isolated talipes equinovarus and a duplication of the ubiquitously transcribed tetratricopeptide repeat gene on X chromosome (UTX) was found to segregate with familial talipes equinovarus. CHD1 recognizes H3K4me and promotes transcriptional elongation of hypomethylated HOX genes in mouse hindlimb fibroblasts.…”

Section: Copy Number Analysis In Talipes Equinovarusmentioning

confidence: 99%

“…CHD1 recognizes H3K4me and promotes transcriptional elongation of hypomethylated HOX genes in mouse hindlimb fibroblasts. 66 UTX is enriched around the transcription start sites of HOX genes in primary human fibroblasts and has been shown to regulate H3K27 methylation at HOX gene promoters. 67 Morpholino inhibition of zebrafish UTX results in misregulation of HOX genes and developmental defects in posterior somitogenesis.…”

Section: Copy Number Analysis In Talipes Equinovarusmentioning

confidence: 99%

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

et al. 2012

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Talipes equinovarus is one of the most common congenital musculoskeletal anomalies and has a worldwide incidence of 1 in 1000 births. A genetic predisposition to talipes equinovarus is evidenced by the high concordance rate in twin studies and the increased risk to first-degree relatives. Despite the frequency of isolated talipes equinovarus and the strong evidence of a genetic basis for the disorder, few causative genes have been identified. To identify rare and/or recurrent copy number variants, we performed a genome-wide screen for deletions and duplications in 413 isolated talipes equinovarus patients using the Affymetrix 6.0 array. Segregation analysis within families and gene expression in mouse E12.5 limb buds were used to determine the significance of copy number variants. We identified 74 rare, gene-containing copy number variants that were present in talipes equinovarus probands and not present in 759 controls or in the Database of Genomic Variants. The overall frequency of copy number variants was similar between talipes equinovarus patients compared with controls. Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2. Although our results do not support a major role for recurrent copy number variations in the etiology of isolated talipes equinovarus, they do suggest a role for genes involved in early embryonic patterning in some families that can now be tested with large-scale sequencing methods. INTRODUCTIONIsolated talipes equinovarus, also called clubfoot, is one of the most common serious congenital birth defects with an estimated birth prevalence of 1 per 1000 live births. 1 Talipes equinovarus consists of malalignment of the bones and joints of the foot and ankle, and is distinguished from positional foot anomalies because it is rigid and not passively correctable (Figure 1). Approximately 20% of talipes equinovarus cases are associated with chromosomal abnormalities, or known genetic syndromes 2,3 and it is a common component of several neurological disorders, including distal arthrogryposis, myotonic dystrophy, and myelomeningocele. Despite the frequency of talipes equinovarus in neurological disorders, no consistent neuromuscular abnormalities have been identified in isolated talipes equinovarus patients using muscle biopsy or electrophysiological examinations. [4][5][6][7] Most cases of clubfeet (80%) occur as isolated birth defects and are considered idiopathic. 8 Approximately 25% of patients with isolated talipes equinovarus report a family history of talipes equinovarus, suggesting a genetic basis for this disorder. 9 Twin studies also support a role for genetic factors, as identical twins have a 33% concordance rate for talipes

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“…The loss of DDM1 leads to a profound decrease of methylation from some TEs and repeats and strong transcriptional activation of TEs (Jeddeloh et al, 1999;Lippman et al, 2004), and inbred ddm1 mutant lines have increased rates of transposition and produce severe developmental abnormalities (Tsukahara et al, 2009). Mutation of Lsh, the mouse homolog of DDM1, causes similar methylation phenotypes (Tao et al, 2010). Recent data indicate that Arabidopsis DDM1 is important for DNA methylation in TEs, and the strength of the DDM1 requirement is positively correlated with heterochromatin (Zemach et al, 2013).…”

mentioning

confidence: 99%

Analysis of Chromatin Regulators Reveals Specific Features of Rice DNA Methylation Pathways

Tan

Zhou²,

Zhou³

et al. 2016

Plant Physiol.

113

157

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Plant DNA methylation that occurs at CG, CHG, and CHH sites (H = A, C, or T) is a hallmark of the repression of repetitive sequences and transposable elements (TEs). The rice (Oryza sativa) genome contains about 40% repetitive sequence and TEs and displays specific patterns of genome-wide DNA methylation. The mechanism responsible for the specific methylation patterns is unclear. Here, we analyzed the function of OsDDM1 (Deficient in DNA Methylation 1) and OsDRM2 (Deficient in DNA Methylation 1) in genome-wide DNA methylation, TE repression, small RNA accumulation, and gene expression. We show that OsDDM1 is essential for high levels of methylation at CHG and, to a lesser extent, CG sites in heterochromatic regions and also is required for CHH methylation that mainly locates in the genic regions of the genome. In addition to a large member of TEs, loss of OsDDM1 leads to hypomethylation and up-regulation of many protein-coding genes, producing very severe growth phenotypes at the initial generation. Importantly, we show that OsDRM2 mutation results in a nearly complete loss of CHH methylation and derepression of mainly small TE-associated genes and that OsDDM1 is involved in facilitating OsDRM2-mediated CHH methylation. Thus, the function of OsDDM1 and OsDRM2 defines distinct DNA methylation pathways in the bulk of DNA methylation of the genome, which is possibly related to the dispersed heterochromatin across chromosomes in rice and suggests that DNA methylation mechanisms may vary among different plant species.DNA methylation in flowering plants occurs in three sequence contexts: the so-called symmetric CG and CHG and the asymmetric CHH, where H is any nucleotide except G. Methylation in each context is believed to be catalyzed primarily by a specific family of DNA methyltransferases: MET1 (homologous to animal Dnmt1) for CG, plant-specific chromomethylases (CMT3 and CMT2) for CHG, and DRM2 (homologous to animal Dnmt3) for CHH (Law and Jacobsen, 2010).Recently, it was shown that CMT2 is a major CHH methyltransferase in Arabidopsis (Arabidopsis thaliana; Zemach et al., 2013;Stroud et al., 2014). The majority of plant methylation is found in transposable elements (TEs) and transcribed TE genes (known as transposable element-related genes [TEGs]) and is crucial for the repression of TE expression and transposition (Law and Jacobsen, 2010). Substantial methylation also is found in the bodies of active genes, where methylation is generally restricted to the CG context (Law and Jacobsen, 2010;Zemach et al., 2010). Methylation in all sequence contexts also is found in the promoter regions of many genes, which represses gene expression.In Arabidopsis, the maintenance of CHH methylation is mediated by RNA-directed DNA methylation (RdDM) involving the methyltransferase activity of DRM2 (Law and Jacobsen, 2010). DNA methylation also is influenced by chromatin factors. For instance, the Arabidopsis Snf2 family nucleosome remodeler DDM1, which can shift nucleosomes in vitro (Brzeski and Jerzmanowski, 2003), is essential fo...

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Lsh Mediated RNA Polymerase II Stalling at HoxC6 and HoxC8 Involves DNA Methylation

Cited by 42 publications

References 59 publications

Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis

Cigarette smoke mediates epigenetic repression of miR-487b during pulmonary carcinogenesis

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

Analysis of Chromatin Regulators Reveals Specific Features of Rice DNA Methylation Pathways

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