Genomic and Proteomic Resolution of Heterochromatin and Its Restriction of Alternate Fate Genes.
Genomic and Proteomic Resolution of Heterochromatin and Its Restriction of Alternate Fate Genes.
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DOI：
10.1016/j.molcel.2017.11.030
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发表时间：
2017-12-21
期刊：
影响因子：
16
通讯作者：
Zaret KS
中科院分区：
文献类型：
--
作者：
Becker JS;McCarthy RL;Sidoli S;Donahue G;Kaeding KE;He Z;Lin S;Garcia BA;Zaret KS
异染色质通过阻碍基因的激活来维持细胞的身份。异染色质区与组蛋白3赖氨酸9三甲基化（H3 K9 me 3）或H3 K27 me 3相关，但这些修饰也存在于允许转录的常染色质区。我们发现对超声处理的抗性是异染色质状态的可靠指标，并且我们开发了一种生物物理方法（conventient-seq）来区分超声抗性异染色质（srHC）与常染色质中H3 K9 me 3和H3 K27 me 3结构域的亚型。这些分类比单独的组蛋白标记更准确地预测转录沉默和替代命运基因在直接细胞转化过程中对激活的抗性。我们的H3 K9 me 3标记的srHC和功能筛选的蛋白质组学揭示了不同的蛋白质，包括RBMX和RBMXL 1，在细胞重编程过程中阻碍基因诱导。用测序技术分离srHC提供了一个全基因组的染色质结构图，阐明了阻遏结构域的亚型，这些亚型独特地预测了多种其他染色质特性。
Heterochromatin is integral to cell identity maintenance by impeding the activation of genes for alternate cell fates. Heterochromatic regions are associated with histone 3 lysine 9 trimethylation (H3K9me3) or H3K27me3, but these modifications are also found in euchromatic regions that permit transcription. We discovered that resistance to sonication is a reliable indicator of the heterochromatin state, and we developed a biophysical method (Gradient-seq) to discriminate subtypes of H3K9me3 and H3K27me3 domains in sonication-resistant heterochromatin (srHC) versus euchromatin. These classifications are more accurate than the histone marks alone in predicting transcriptional silence and resistance of alternate-fate genes to activation during direct cell conversion. Our proteomics of H3K9me3-marked srHC and functional screens revealed diverse proteins, including RBMX and RBMXL1, that impede gene induction during cellular reprogramming. Isolation of srHC with Gradient-seq provides a genome-wide map of chromatin structure, elucidating subtypes of repressed domains that are uniquely predictive of diverse other chromatin properties.
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H3K9ME3依赖性异染色质：细胞命运变化的屏障。
DOI：
10.1016/j.tig.2015.11.001
发表时间：
2016-01
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Becker JS;Nicetto D;Zaret KS
通讯作者：
Zaret KS
影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
通讯作者：
Narita, Masashi
DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
16
作者：
Eberl, H. Christian;Spruijt, Cornelia G.;Mann, Matthias
通讯作者：
Mann, Matthias