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・From Environment to [Epi]Genome and Back Again

Environmental Mutagenesis and Genomics Society (EMGS) - 24 Sep 2016



・2016 Synthetic Biology: Engineering, Evolution & Design (SEED)

 http://synbioconference.org/2016    July18-21, 2016






Review  Epigenetics & Chromatin 2015, 8:3

Constitutive heterochromatin formation and transcription in mammals

Nehmé Saksouk, Elisabeth Simboeck and Jérôme Déjardin*


Constitutive heterochromatin, mainly formed at the gene-poor regions of pericentromeres, is believed to ensure a condensed and transcriptionally inert chromatin conformation. Pericentromeres consist of repetitive tandem satellite repeats and are crucial chromosomal elements that are responsible for accurate chromosome segregation in mitosis. The repeat sequences are not conserved and can greatly vary between different organisms, suggesting that pericentromeric functions might be controlled epigenetically. In this review, we will discuss how constitutive heterochromatin is formed and maintained at pericentromeres in order to ensure their integrity. We will describe the biogenesis and the function of main epigenetic pathways that are involved and how they are interconnected. Interestingly, recent findings suggest that alternative pathways could substitute for well-established pathways when disrupted, suggesting that constitutive heterochromatin harbors much more plasticity than previously assumed. In addition, despite of the heterochromatic nature of pericentromeres, there is increasing evidence for active and regulated transcription at these loci, in a multitude of organisms and under various biological contexts. Thus, in the second part of this review, we will address this relatively new aspect and discuss putative functions of pericentromeric expression.


epigenetic factors; heterochromatin; histone modifying enzymes; pericentromere; transcription

2013 Jun;10(6):915-8. doi: 10.4161/rna.24711. Epub 2013 Apr 17.

Sprouts of RNA epigenetics: the discovery of mammalian RNA demethylases.

Zheng G1, Dahl JA, Niu Y, Fu Y, Klungland A, Yang YG, He C.


More than 100 structurally distinct RNA modifications have been identified in all kingdoms of life. These post-transcriptional modifications are widely present in various RNAs, including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), long non-coding RNA (lncRNA), etc. We have shown that the methylation of N(6)-methyladenine (m(6)A) can be reversed through the discovery of the first RNA demethylase, the human fat mass and obesity-associated protein, FTO, in 2011. (Most recently, we have identified a new mammalian RNA demethylase, ALKBH5, which is also able to remove the methyl group of m(6)A from RNA both in vitro and in vivo (Fig. 1A). The ALKBH5 protein colocalizes with nuclear speckles where pre-mRNA processing occurs. This protein is actively involved in mRNA export regulation, in which its demethylation activity seems to play an important role, as well as in RNA synthesis. A knockout of the Alkbh5 gene in mice resulted in impaired male fertility due to compromised spermatogenesis. Importantly, increased m(6)A levels were observed in mRNA isolated from the Alkbh5-knockout mouse organs compared to those from wild-type littermates. RNA-Seq results indicate aberrant gene expression in spermatogenic cells of the seminoferous tubulus of testes from Alkbh5-deficient mice, thereby showing that the loss of the m(6)A demethylase influences gene expression, which, in turn, leads to defects in spermatogenesis and increased apoptosis of meiotic cells. Thus, the discovery of FTO and this new RNA demethylase strongly suggests that the methylation of RNA, like DNA and histone modifications, is dynamically regulated and likely to play broad roles in mammalian cells.


N6- methyladenine; RNA demethylase; RNA epigenetics; reversible RNA methylation


環境エピゲノミクス (EEG)研究会の設立について

  ポストゲノム時代を迎え、“Epigenetics”という概念が重要視されつつあります。これはこれまで研究されてきた突然変異に加えて、遺伝子の発現調節や遺伝子の安定性を重視する考え方で、生物学、毒性学、臨床医学、さらに社会学をも変革させる可能性を秘めている重要な概念です。とくに、種々の環境要因と遺伝子発現との相互反応を研究する”Environmental Epigenomics (EEG)の重要性が、毒性学や臨床医学などの分野で認められつつあります。 そこで、主に日本環境変異学(JEMS)に所属する有志が集まり、種々の毒性を“Epigenetics”をkey wordとして考察してゆく原学会(JEMS)に所属する有志が集まり、種々の毒性事象を“Epigenonics”をkey wordとして討議する場として、“環境エピゲノミクス研究会 (EEG)”を設立いたしました。今後は、「環境ホルモン学会」や「環境毒性研究会」などの会員の皆様にもご参加をいただき、種々の環境要因が誘発するさまざまな毒性事象を、“Epigenetics”という概念を基本にして、「環境Epigenomics」という新しい毒性学の概念の確立を目指して活動する予定この研究会は、「環境ホルモン学会」や「環境毒性研究会」などの会員の皆様にもご参加いただき、さまざまな環境要因が誘発するさまざまな毒性事象から、「環境Epigenomics」という新しい環境毒性学の構築を目指して活動してゆく所存です。 研究会は原則として年2回、定例会およびJEMS学会開催時に実施する予定です。また、ホームページ(http//eegs.web.fc2.com/)を媒体として、研究会の活動や関連学会の情報、さらにこの分野での文献情報なども提供する予定です。この分野に関心をお持ちの多数のの研究者にご参加をいただき、積極的な討論を通して、この分野の発展にいささかなりとも貢献できればと思っております。 どうか、以上の趣旨をご理解いただき、多くの方々にこの研究会にご入会いただきたいと思います。

"Environmental Epigenomics(環境ゲノム発現撹乱)” への招待

                                  澁谷 徹 (“Tox21” 研究所)  (t.shibuya.tox21@zpost.plala.or.jp


Figure 1. Waddington’s Classical Epigenetic Landscape
In 1957, Conrad Waddington proposed the concept of an epigenetic
landscape to represent the process of cellular decision-making during
development. At various points in this dynamic visual metaphor,
the cell (represented by a ball) can take specific permitted trajectories,
leading to different outcomes or cell fates. Figure reprinted from
Waddington, 1957.

Figure 2. A Current View of the Epigenetic Molecular
Known factors that regulate epigenetic phenomena are shown directing
the complex movement of pinballs (cells) across the elegant landscape
proposed by Waddington (see Figure 1). No specific order of molecular
events is implied; as such a sequence remains unknown. Effector
proteins recognize specific histone modifications, while presenters are
proposed to impart substrate specificity for histone-modifying enzymes
(Ruthenburg et al., 2007). H3.3 and macroH2A are shown only as representative
histone variants involved in transcriptional activation or repression,
respectively. For simplicity, other histone (and nonhistone) proteins
are not shown. (ChR, chromatin remodelers; DNMTs, DNA methyltransferases;
HATs, histone acetyltransferases; HDACs, histone deacetylases;
HMTs, histone methyltransferases; HDMs, histone demethylases; DDMs,
DNA demethylases [unidentified in mammals to date]; and TFs, transcription
factors [reflecting the genetic component of the epigenetic process].)
Illustration by Sue Ann Fung-Ho.













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