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16
A bivalent chromatin structure marks key developmental genes in embryonic stem cells, Cell 125
, 2006
"... The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by ex ..."
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The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed ‘‘bivalent domains,’ ’ consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.
HY: Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs
- Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang
"... Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kil ..."
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Cited by 194 (3 self)
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Noncoding RNAs (ncRNA) participate in epigenetic regulation but are poorly understood. Here we characterize the transcriptional landscape of the four human HOX loci at five base pair resolution in 11 anatomic sites and identify 231 HOX ncRNAs that extend known transcribed regions by more than 30 kilobases. HOX ncRNAs are spatially expressed along developmental axes and possess unique sequence motifs, and their expression demarcates broad chromosomal domains of differential histone methylation and RNA polymerase accessibility. We identified a 2.2 kilobase ncRNA residing in the HOXC locus, termed HOTAIR, which represses transcription in trans across 40 kilobases of the HOXD locus. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is required for PRC2 occupancy and histone H3 lysine-27 trimethylation of HOXD locus. Thus, transcription of ncRNA may demarcate chromosomal domains of gene silencing at a distance; these results have broad implications for gene regulation in development and disease states.
SPECIALITE: GENETIQUE
, 2011
"... Je tiens à remercier l‟ensemble des personnes qui m‟ont entouré et accompagné dans la réalisation, l‟écriture et l‟expertise de cette thèse. Tout d‟abord, je tiens à remercier Judith Landman-Parker et Guy Leverger, pour m‟avoir encouragé à entreprendre un travail de recherche sur la leucémogénèse et ..."
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Je tiens à remercier l‟ensemble des personnes qui m‟ont entouré et accompagné dans la réalisation, l‟écriture et l‟expertise de cette thèse. Tout d‟abord, je tiens à remercier Judith Landman-Parker et Guy Leverger, pour m‟avoir encouragé à entreprendre un travail de recherche sur la leucémogénèse et soutenu dans l‟écriture de cette thèse durant mon clinicat. Je remercie Olivier Bernard de m‟avoir accepté dans son laboratoire, conseillé et accompagné, notamment dans l‟élaboration des PCR et des différents clonages. tel-00649445, version 1- 8 Dec 2011 Merci à Serge Romana d‟avoir accepté de m‟encadrer pour la réalisation du master, puis de ma thèse, et de m‟avoir permis de participer à ce travail collaboratif sur l‟étude des fusions NUP98 dans les hémopathies malignes humaines. Merci à Xinying Su qui a assuré la lourde tâche de m‟accueillir et de m‟encadrer pour mes premiers travaux nécessitant l‟utilisation des techniques de PCR. Merci à Christine Ragu qui m‟a secondé et accompagné dans l‟apprentissage de la cytométrie en flux et dans l‟approche expérimentale animale, malgré son lourd travail de
Certified by............................................................................................................................................
, 2009
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AID, activation-induced
"... S region sequence, RNA polymerase II, and histone modifications create chromatin ..."
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S region sequence, RNA polymerase II, and histone modifications create chromatin
JCB: COMMENT Epigenetics, Wnt signaling, and stem cells: the
"... Stem cells use both transcriptional and epigenetic mechanisms to control gene expression and regulate tissue development and homeostasis. In this issue, Gu et al. (Gu, ..."
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Stem cells use both transcriptional and epigenetic mechanisms to control gene expression and regulate tissue development and homeostasis. In this issue, Gu et al. (Gu,
IN GENE REGULATION AND CELL CYCLE
, 2009
"... I would like taking this opportunity to express my deep gratitude to Dr ..."
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Journal of Visualized Experiments www.jove.com Video Article
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and reproduction in any medium, provided the original work is properly cited.
Functional Demarcation of Active and
, 2014
"... We are pleased to present a series of Annotated Classics celebrating 40 years of exciting biology in the pages of Cell. This install- ..."
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We are pleased to present a series of Annotated Classics celebrating 40 years of exciting biology in the pages of Cell. This install-