Nature子刊：三篇文章鉴别可拓展“核染质编码”两种新变异
生物谷推荐英文原文
英文原文二：
Published online: 9 December 2007; | doi:10.1038/ncb1671Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex
Iain W. McKinnell1, 3, Jeff Ishibashi1, 3, Fabien Le Grand1, Vincent G. J. Punch1, Gregory C. Addicks1, Jack F. Greenblatt2, F. Jeffrey Dilworth1 & Michael A. Rudnicki1
1 Sprott Centre for Stem Cell Research, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6 and Department of Medicine, University of Ottawa, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. 2 Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Ontario, Canada M5G 1L6. 3 These authors contributed equally to this work. Correspondence should be addressed to Michael A. Rudnicki mrudnicki@ohri.ca Satellite cells purified from adult skeletal muscle can participate extensively in muscle regeneration and can also re-populate the satellite cell pool, suggesting that they have direct therapeutic potential for treating degenerative muscle diseases1, 2. The paired-box transcription factor Pax7 is required for satellite cells to generate committed myogenic progenitors3. In this study we undertook a multi-level approach to define the role of Pax7 in satellite cell function. Using comparative microarray analysis, we identified several novel and strongly regulated targets; in particular, we identified Myf5 as a gene whose expression was regulated by Pax7. Using siRNA, fluorescence-activated cell sorting (FACS) and chromatin immunoprecipitation (ChIP) studies we confirmed that Myf5 is directly regulated by Pax7 in myoblasts derived from satellite cells. Tandem affinity purification (TAP) and mass spectrometry were used to purify Pax7 together with its co-factors. This revealed that Pax7 associates with the Wdr5–Ash2L–MLL2 histone methyltransferase (HMT) complex that directs methylation of histone H3 lysine 4 (H3K4, refs 4–10). Binding of the Pax7–HMT complex to Myf5 resulted in H3K4 tri-methylation of surrounding chromatin. Thus, Pax7 induces chromatin modifications that stimulate transcriptional activation of target genes to regulate entry into the myogenic developmental programme. 英文原文三： Published online: 9 December 2007; | doi:10.1038/ncb1674 Epigenetic memory of an active gene state depends on histone H3.3 incorporation into chromatin in the absence of transcription Ray Kit Ng1, 2 & J. B. Gurdon1
1 Wellcome Trust/Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK and Department of Zoology, University of Cambridge, UK 2 Present address: Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB22 3AT, UK Correspondence should be addressed to J. B. Gurdon j.gurdon@gurdon.cam.ac.uk The remarkable stability of gene expression in somatic cells is exemplified by the way memory of an active gene state is retained when an endoderm cell nucleus is transplanted to an enucleated egg1. Here we analyse the mechanism of a similar example of epigenetic memory. We find that memory can persist through 24 cell divisions in the absence of transcription and applies to the expression of the myogenic gene MyoD in non-muscle cell lineages of nuclear transplant embryos. We show that memory is not explained by the methylation of promoter DNA. However, we demonstrate that epigenetic memory correlates with the association of histone H3.3 with the MyoD promoter in embryos that display memory but not in those where memory has been lost. The association of a mutated histone H3.3 (H3.3 E4, which lacks the methylatable H3.3 lysine 4) with promoter DNA eliminates memory, indicating a requirement of H3.3 K4 for memory. We also show that overexpression of H3.3 can enhance memory in transplanted nuclei. We therefore conclude that the association of histone H3.3 with the MyoD promoter makes a necessary contribution to this example of memory. Hence, we suggest that epigenetic memory helps to stabilize gene expression in normal development; it might also help to account for the inefficient reprogramming in some transplanted nuclei.
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