Epigenetic regulation of development by histone lysine methylation

Dambacher, Silvia; Hahn, Matthias; Schotta, Gunnar

doi:10.1038/hdy.2010.49

Cited by 89 publications

(86 citation statements)

References 135 publications

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“…The epigenetic regulatory functions of MLL family proteins have gained interests in recent years (Dambacher et al, 2010). MLL1 and MLL2 were shown to methylate histone H3 Lys4 (H3K4) by forming histone methyltransferase complexes consisting of WDR5, RbBP5 and ASH2L (Hughes et al, 2004;Yokoyama et al, 2004;Wysocka et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53

et al. 2011

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Mixed lineage leukemia 5 (MLL5) has been implicated in multiple aspects of cell physiology, such as hematopoiesis, cell cycle control and chromatin regulatory network. In this study, we present evidence that MLL5 is involved in the camptothecin (CPT)-induced p53 activation. CPT promoted the degradation of MLL5 protein in a time-and dose-dependent manner in actively replicating cells. The downregulation of MLL5 led to phosphorylation of p53 at Ser392, which was abrogated by exogenous overexpression of MLL5. In MLL5-knockdown cells, p53 protein was stabilized and bound to DNA with higher affinity, leading to activation of downstream genes. Co-immunoprecipitation showed that MLL5 preferentially interacted with the tetramerized form of p53, and knockdown of MLL5 promoted chromatin accumulation of p53 tetramers, suggesting that the association of MLL5 with p53 may prevent the p53 tetramers from binding to the chromatin target sites. The role of MLL5 in CPT-induced p53 activation was conserved in developing zebrafish, where CPT downregulated zebrafish Mll5 protein, and the microinjection of zebrafish mll5 mRNA substantially blocked the CPT-induced apoptosis. In summary, our study proposed MLL5 as a novel component in the regulation of p53 homeostasis and a new cellular determinant of CPT.

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Section: Introductionmentioning

confidence: 99%

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53

et al. 2011

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“…Methylation marks are attached to the histones of the nucleosomes by methyltransferases and are removed by demethylases (Dambacher et al, 2010). Interestingly, removal of repressive methylation marks is necessary for the neural crest specification program.…”

Section: Epigenetic Regulation In Neural Crest Formationmentioning

confidence: 99%

Establishing neural crest identity: a gene regulatory recipe

2015

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The neural crest is a stem/progenitor cell population that contributes to a wide variety of derivatives, including sensory and autonomic ganglia, cartilage and bone of the face and pigment cells of the skin. Unique to vertebrate embryos, it has served as an excellent model system for the study of cell behavior and identity owing to its multipotency, motility and ability to form a broad array of cell types. Neural crest development is thought to be controlled by a suite of transcriptional and epigenetic inputs arranged hierarchically in a gene regulatory network. Here, we examine neural crest development from a gene regulatory perspective and discuss how the underlying genetic circuitry results in the features that define this unique cell population.

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“…Trimethylation of lysine 4 (H3K4me3) relates to trithorax-Group (trx-G) action (Roguev et al, 2001) and is a hallmark of active promoters (Santos-Rosa et al, 2002;Bannister and Kouzarides, 2011). H3K4me3 is opposed by repression through H3K27me3 mediated by Polycomb-Group (Pc-G) action (Voigt et al, 2012) and H3K9me2/3, which defines heterochromatin (Peters et al, 2001), whereas H3K36me3 is mainly found in transcribed regions due to the association of the major H3K36 methyltransferase with the elongating RNA Polymerase II through phosphorylation of serine 2 of its CTD tail (Li et al, 2003;Schaft et al, 2003;Dambacher et al, 2010). Recent data on growing oocytes indicates that local deposition of H3K36me3 and removal of H3K4me2/me3 sets the stage for de novo DNA methylation (Stewart et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program

et al. 2017

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Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility in mice. Oocyte-specific Gdf9-iCre conditional knockout (Setd1b Gdf9 cKO) ovaries develop through all stages; however, follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle. Most Setd1b Gdf9 cKO zygotes remained in the pronuclear stage and displayed polyspermy in the perivitelline space. Expression profiling of Setd1bGdf9 cKO MII oocytes revealed (1) that Setd1b promotes the expression of the major oocyte transcription factors including Obox1, 2, 5, 7, Meis2 and Sall4; and (2) twice as many mRNAs were upregulated than downregulated, suggesting that Setd1b also promotes the expression of negative regulators of oocyte development with multiple Zfp-KRAB factors implicated. Together, these findings indicate that Setd1b serves as maternal effect gene through regulation of the oocyte gene expression program.

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Epigenetic regulation of development by histone lysine methylation

Cited by 89 publications

References 135 publications

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53

Camptothecin-induced downregulation of MLL5 contributes to the activation of tumor suppressor p53

Establishing neural crest identity: a gene regulatory recipe

Setd1b, encoding a histone 3 lysine 4 methyltransferase, is a maternal effect gene required for the oogenic gene expression program

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