Gateways to the FANTOM5 promoter level mammalian expression atlas

Lizio, Marina; Harshbarger, Jayson; Shimoji, Hisashi; Severin, Jessica; Kasukawa, Takeya; Sahin, Serkan; Abugessaisa, Imad; Fukuda, Shiro; Hori, Fumi; Ishikawa-Kato, Sachi; Mungall, Christopher J.; Arner, Peter; Baillie, J Kenneth; Bertin, Nicolas; Bono, Hidemasa; Hoon, Michiel de; Diehl, Alexander D.; Dimont, Emmanuel; Freeman, Tom C.; Fujieda, Kaori; Hide, Winston; Kaliyaperumal, Rajaram; Katayama, Toshiaki; Lassmann, Timo; Meehan, Terrence F.; Nishikata, Koro; Hiromasa, Ono; Rehli, Michael; Sandelin, Albin; Schultes, Erik; Hoen, Peter A.C. ‘t; Tatum, Zuotian; Thompson, Mark; Toyoda, Tetsuro; Wright, Derek W.; Daub, Carsten O.; Itoh, Masayoshi; Carninci, Piero; Hayashizaki, Yoshihide; Kawaji, Hideya

doi:10.1186/s13059-014-0560-6

Cited by 760 publications

(767 citation statements)

References 67 publications

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“…41 Copper is known to regulate iron utilization in the bone marrow and in hemoglobin synthesis. [42][43][44][45] Importantly, both ABCB7 and ATP7A genes are expressed in the bone marrow 26,46 and in various tissues (Illumina Human Body Map 2.0), 26,46,47 (Supplementary Figure 5). Given the mutual regulatory influence of the copper and iron uptake, the clinical phenotype described in the Buryat patients may depend on presumable interaction of genetic defects in two genes for the MBPs in some tissue cells, an interesting case of syndrome inherited as a X-linked monogenic trait.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

et al. 2015

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X-linked congenital cerebellar ataxia is a heterogeneous nonprogressive neurodevelopmental disorder with onset in early childhood. We searched for a genetic cause of this condition, previously reported in a Buryat pedigree of Mongolian ancestry from southeastern Russia. Using whole-genome sequencing on Illumina HiSeq 2000 platform, we found a missense mutation in the ABCB7 (ABC-binding cassette transporter B7) gene, encoding a mitochondrial transporter, involved in heme synthesis and previously associated with sideroblastic anemia and ataxia. The mutation resulting in a substitution of a highly conserved glycine to serine in position 682 is apparently a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. Moreover, in these affected men we also found the genetic defects in two other genes closely linked to ABCB7 on chromosome X: a deletion of a genomic region harboring the second exon of copper-transporter gene (ATP7A) and a complete deletion of PGAM4 (phosphoglycerate mutase family member 4) retrogene located in the intronic region of the ATP7A gene. Despite the deletion, eliminating the first of six metal-binding domains in ATP7A, no signs for Menkes disease or occipital horn syndrome associated with ATP7A mutations were found in male carriers. The role of the PGAM4 gene has been previously implicated in human reproduction, but our data indicate that its complete loss does not disrupt male fertility. Our finding links cerebellar pathology to the genetic defect in ABCB7 and ATP7A structural variant inherited as X-linked trait, and further reveals the genetic heterogeneity of X-linked cerebellar disorders.

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Section: Discussionmentioning

confidence: 99%

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

et al. 2015

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“…epigenomics roadmap,97, 98 FANTOM99, 100, 101, 102). In the post‐GWAS era, there are very strong data linking genetic variation (single nucleotide polymorphism or snp) in a wide variety of immunological disease cohorts, but identification of individual causal target genes has been difficult, as it is now apparent that the majority of this genetic variation does not disrupt the coding region of genes, but is located in noncoding regions 103.…”

Section: Genetic Risk Of Autoimmune Disease Alters Treg Functionmentioning

confidence: 99%

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

et al. 2018

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Regulatory T cells (Treg) are critical for preventing autoimmunity and curtailing responses of conventional effector T cells (Tconv). The reprogramming of T‐cell fate and function to generate Treg requires switching on and off of key gene regulatory networks, which may be initiated by a subtle shift in expression levels of specific genes. This can be achieved by intermediary regulatory processes that include microRNA and long noncoding RNA‐based regulation of gene expression. There are well‐documented microRNA profiles in Treg and Tconv, and these can operate to either reinforce or reduce expression of a specific set of target genes, including FOXP3 itself. This type of feedforward/feedback regulatory loop is normally stable in the steady state, but can alter in response to local cues or genetic risk. This may go some way to explaining T‐cell plasticity. In addition, in chronic inflammation or autoimmunity, altered Treg/Tconv function may be influenced by changes in enhancer–promoter interactions, which are highly cell type‐specific. These interactions are impacted by genetic risk based on genome‐wide association studies and may cause subtle alterations to the gene regulatory networks controlled by or controlling FOXP3 and its target genes. Recent insights into the 3D organisation of chromatin and the mapping of noncoding regulatory regions to the genes they control are shedding new light on the direct impact of genetic risk on T‐cell function and susceptibility to inflammatory and autoimmune conditions.

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“…However, large-scale genome-wide analysis projects such as ENCODE 131,132 and FANTOM5 (REF. 133) showed that distant regulatory enhancers also undergo CpG methylation. Enhancer methylation in RCC has been analysed at the genome scale, and one study in particular identified an enrichment of aberrant enhancer methylation associated with networks involved in the cellular response to hypoxia 134 .…”

Section: Non-promoter Dna Methylationmentioning

confidence: 99%

The epigenetic landscape of renal cancer

2016

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| The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers.

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Gateways to the FANTOM5 promoter level mammalian expression atlas

Cited by 760 publications

References 67 publications

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

Unravelling the molecular basis for regulatory T‐cell plasticity and loss of function in disease

The epigenetic landscape of renal cancer

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