A long-range cis-regulatory element for class I odorant receptor genes

Iwata, Tetsuo; Niimura, Yoshihito; Kobayashi, Chizuru; Shirakawa, Daichi; Suzuki, Haruna; Enomoto, Takayuki; Touhara, Kazushige; Yoshihara, Yoshihiro; Hirota, Junji

doi:10.1038/s41467-017-00870-4

Cited by 32 publications

(67 citation statements)

References 41 publications

(73 reference statements)

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“…Enhancers can also impact each other at larger distances, such as PU.1 autoregulation in myeloid cells, where C/EBPa binds to an enhancer 14 kb upstream of PU.1 and promotes the activation and accessibility of a neighboring enhancer 2 kb downstream of the predominant enhancer (Leddin et al, 2011). Similar enhancer hierarchies between individual enhancers have recently been described in other systems (Huang et al, 2018;Iwata et al, 2017), and our genome-wide observations suggest that these hierarchies are likely a consistent feature of estrogen-dependent gene regulation.…”

Section: Discussionmentioning

confidence: 68%

Regulatory Sharing Between Estrogen Receptor α Bound Enhancers

Carleton

Ginley-Hidinger

Berrett

et al. 2020

Preprint

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The human genome encodes an order of magnitude more gene expression enhancers than promoters, suggesting that most genes are regulated by the combined action of multiple enhancers. We have previously shown that neighboring estrogen-responsive enhancers, which are approximately 5,000 basepairs apart, exhibit complex synergistic contributions to the production of an estrogenic transcriptional response. Here we sought to determine the molecular underpinnings of the observed enhancer cooperativity. We generated genetic deletions of individual estrogen receptor a (ER) bound enhancers and found that enhancers containing full estrogen response element (ERE) motifs control ER binding at neighboring sites, while enhancers with pre-existing histone acetylation/accessibility confer a permissible chromatin environment to the neighboring enhancers. Genome engineering revealed that a cluster of two enhancers with half EREs could not compensate for the lack of a full ERE site within the cluster. In contrast, two enhancers with full EREs produced a transcriptional response greater than the wild-type locus. By swapping genomic sequences between enhancers, we found that the genomic location in which a full ERE resides strongly influences enhancer activity. Our results lead to a model in which a full ERE is required for ER recruitment, but the presence of a pre-existing active chromatin environment within an enhancer cluster is also needed in order for estrogen-driven gene regulation to occur.

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Section: Discussionmentioning

confidence: 68%

Regulatory Sharing Between Estrogen Receptor α Bound Enhancers

Carleton

Ginley-Hidinger

Berrett

et al. 2020

Preprint

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“…ORs are distributed in clusters on most mammalian chromosomes. There are strong indications of a common ancestry for most OR clusters [5], a feature which might be related to common cis-regulatory elements [6,7]. Nevertheless, processes of gene duplication and gene deletion have taken place in each species [1][2][3][4], making orthology relationships difficult to determine [8], and hence requiring careful manual curation for the assignment of gene nomenclature.…”

Section: Introductionmentioning

confidence: 99%

A unified nomenclature for vertebrate olfactory receptors

et al. 2020

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Background: Olfactory receptors (ORs) are G protein-coupled receptors with a crucial role in odor detection. A typical mammalian genome harbors~1000 OR genes and pseudogenes; however, different gene duplication/ deletion events have occurred in each species, resulting in complex orthology relationships. While the human OR nomenclature is widely accepted and based on phylogenetic classification into 18 families and further into subfamilies, for other mammals different and multiple nomenclature systems are currently in use, thus concealing important evolutionary and functional insights. Results: Here, we describe the Mutual Maximum Similarity (MMS) algorithm, a systematic classifier for assigning a human-centric nomenclature to any OR gene based on inter-species hierarchical pairwise similarities. MMS was applied to the OR repertoires of seven mammals and zebrafish. Altogether, we assigned symbols to 10,249 ORs. This nomenclature is supported by both phylogenetic and synteny analyses. The availability of a unified nomenclature provides a framework for diverse studies, where textual symbol comparison allows immediate identification of potential ortholog groups as well as species-specific expansions/deletions; for example, Or52e5 and Or52e5b represent a rat-specific duplication of OR52E5. Another example is the complete absence of OR subfamily OR6Z among primate OR symbols. In other mammals, OR6Z members are located in one genomic cluster, suggesting a large deletion in the great ape lineage. An additional 14 mammalian OR subfamilies are missing from the primate genomes. While in chimpanzee 87% of the symbols were identical to human symbols, this number decreased to~50% in dog and cow and to~30% in rodents, reflecting the adaptive changes of the OR gene superfamily across diverse ecological niches. Application of the proposed nomenclature to zebrafish revealed similarity to mammalian ORs that could not be detected from the current zebrafish olfactory receptor gene nomenclature. Conclusions: We have consolidated a unified standard nomenclature system for the vertebrate OR superfamily. The new nomenclature system will be applied to cow, horse, dog and chimpanzee by the Vertebrate Gene Nomenclature Committee and its implementation is currently under consideration by other relevant species-specific nomenclature committees.

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“…Os genes OR são expressos de forma desigual no MOE, sendo alguns ORs escolhidos para serem expressos, mais frequentemente que outros (IBARRA-SORIA et al, 2017;YOUNG et al, 2003 CLOWNEY et al, 2011;IWATA et al, 2017; (BOZZA et al, 2009;IWATA et al, 2017;SERIZAWA et al, 2003), como em trans, por meio do agrupamento de múltiplos enhancers localizados a menos de 100kb de distância de clusters de genes OR em diversos cromossomos (MARKENSCOFF-PAPADIMITRIOU et al, 2014). Assim como as regiões promotoras dos genes OR, os enhancers também são caracterizados pela presença de sítios de ligação HD e O/E-like (IWATA et al, 2017;NISHIZUMI et al, 2007). (SAXONOV et al, 2006).…”

Section: Expressão Do Gene Olfr17 Em Diferentes Contextos Genéticosunclassified

“…Mais recentemente, foi descrita a existência de outro enhancer (elemento J) que teria a função de regular, exclusivamente, a expressão de ORs classe I, expressos apenas na zona 1 (região mais dorsal do MOE)(IWATA et al, 2017). Todos esses achados não permitem, contudo, Recentemente, foi descrito que genes de uma classe de quimiorreceptores expressos em neurônios olfatórios, os TAARs (trace amine-associated receptors), encontram-se associados à periferia nuclear próximos à carioteca(YOON et al, …”

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“…No entanto, a descoberta do elemento J, que controla exclusivamente a expressão dos ORs classe I(IWATA et al, 2017), sugere que o padrão de expressão por zonas pode ser governado pelos enhancers.Ao contrário da maior parte das regiões promotoras no genoma de mamíferos, os promotores de genes OR são curiosamente ricos em nucleotídeos de adenina e timina(CLOWNEY et al, 2011), sugerindo que pode haver elementos regulatórios não canônicos controlando a expressão desses genes. Além dos genes OR, foi verificado que genes do sistema imune e de resposta a xenobióticos também possuem elevados níveis de AT na região promotora.…”

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A influência de polimorfismos de base única na metilação de DNA em genes de receptores olfatórios

Silva¹

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A long-range cis-regulatory element for class I odorant receptor genes

Cited by 32 publications

References 41 publications

Regulatory Sharing Between Estrogen Receptor α Bound Enhancers

Regulatory Sharing Between Estrogen Receptor α Bound Enhancers

A unified nomenclature for vertebrate olfactory receptors

A influência de polimorfismos de base única na metilação de DNA em genes de receptores olfatórios

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