一周快讯：本周表观文献精选（2017.9.16）

23Plus · 公众号 · 生物 · 2017-09-16 07:00

正文

编者按

本周我们精选了近一周发表的优秀文献与你共享，如果你对我们选取的文献有自己深入的解读和见解，欢迎投稿【Plus深读】栏目，在23plus上分享你的视角和思维，这是一个展示的舞台，也许也是一段友情，一次合作的起点哦！

文末有彩蛋，记得看下去哦！

Nature communications

The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3

Eun Shik Choi, Youngseo Cheon, Keunsoo Kang & Daeyoup Lee

https://www.nature.com/articles/s41467-017-00704-3

以裂殖酵母为研究对象，研究了细胞增殖过程中着丝粒上组蛋白H3变体CENP-A替代H3的调控机理。

Abstract：

The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregati on. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1. CENP-ACnp1 chromatin actively recruits the Ino80 complex to centromeres to elicit eviction of histone H3-containing nucleosomes. Artificial targeting of Ino80 subunits to a non-centromeric DNA sequence placed in a native centromere enhances the spreading of CENP-ACnp1 chromatin into the non-centromeric DNA. Based on these results, we propose that CENP-ACnp1 chromatin employs the Ino80 complex to mediate the replacement of histone H3 with CENP-ACnp1, and thereby reinforces itself.

DOI:10.1038/s41467-017-00704-3

Cell Host & Microbe

Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption

Kymberleigh A. Romano, Ana Martinez-del Campo, ……, Emily P. Balskus , and Federico E. Rey

http://www.cell.com/cell-host-microbe/pdfExtended/S1931-3128(17)30304-9

以胆碱的代谢为切入点，研究了肠道微生物对宿主代谢、表观遗传及行为的影响。

Abstract：

Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.

DOI:http://dx.doi.org/10.1016/j.chom.2017.07.021

Cell

Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition

Erica Korb, Margaret Herre, Ilana Zucker-Scharff, Jodi Gresack, C. David Allis, Robert B. Darnell

http://www.cell.com/cell/fulltext/S0092-8674(17)30869-3

本文主要研究了脆性X综合征（一种遗传病）相关转录表达调控的分子机理，为疾病的治疗提供方向。

Abstract：

Fragile X syndrome (FXS) is a leading genetic cause of intellectual disability and autism. FXS results from the loss of function of fragile X mental retardation protein (FMRP), which represses translation of target transcripts. Most of the well-characterized target transcripts of FMRP are synaptic proteins, yet targeting these proteins has not provided effective treatments. We examined a group of FMRP targets that encode transcriptional regulators, particularly chromatin-associated proteins. Loss of FMRP in mice results in widespread changes in chromatin regulation and aberrant gene expression. To determine if targeting epigenetic factors could reverse phenotypes associated with the disorder, we focused on Brd4, a BET protein and chromatin reader targeted by FMRP. Inhibition of Brd4 function alleviated many of the phenotypes associated with FXS. We conclude that loss of FMRP results in significant epigenetic misregulation and that targeting transcription via epigenetic regulators like Brd4 may provide new treatments for FXS.

DOI: http://dx.doi.org/10.1016/j.cell.2017.07.033

Cancer Cell

Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations

Michelle Vaz, Stephen Y. Hwang,……, Hariharan P. Easwaran, * and Stephen B. Baylin

http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30349-5

以长期吸烟对肺癌早期进程的影响为研究主题，研究了表观遗传变化和基因突变在这一过程中是如何协同作战的。

Abstract：

We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer. These cells, in the absence of any driver gene mutations, now transform by introducing a single KRAS mutation and form adenosquamous lung carcinomas in mice. Thus, epigenetic abnormalities may prime for changing oncogene senescence to addiction for a single key oncogene involved in lung cancer initiation.

DOI: http://dx.doi.org/10.1016/j.ccell.2017.08.006

Nature methods

An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues

M Ryan Corces, Alexandro E Trevino,……, William J Greenleaf & Howard Y Chang

https://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.4396.html

介绍了一款优化的ATAC-seq技术，可用于研究冷冻组织切片中疾病相关的DNA元件，可用于分析微量样品。

Abstract：

We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC protocol generates chromatin accessibility profiles from archival frozen tissue samples and 50-μm sections, revealing the activities of disease-associated DNA elements in distinct human brain structures. The Omni-ATAC protocol enables the interrogation of personal regulomes in tissue context and translational studies.

DOI:10.1038/nmeth.4396

一周快讯：本周表观文献精选（2017.9.16）

正文

请到「今天看啥」查看全文