文章一

Regulatory landscape fusion in rhabdomyosarcoma through interactions between the PAX3 promoter and FOXO1 regulatory elements

横纹肌肉瘤的DNA融合后染色质结构调控研究

Cristina Vicente-García, Barbara Villarejo-Balcells, Ibai Irastorza-Azcárate, Silvia Naranjo, Rafael D. Acemel, Juan J. Tena, Peter W. J. Rigby, Damien P. Devos,Jose L. Gómez-Skarmeta and Jaime J. Carvajal

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1225-z

【导读】基因组结构中红极一时的拓扑结构域,被公认很难通过功能学的扰乱、拯救途径去验证它们的真实性。今年三月Science发表的一篇酵母合成染色体通过分析打乱的酵母合成染色体的3D结构,初步探索了人工合成的结构对基因组的3D机构有些什么影响。本周Genome Biology发表的这篇横纹肌肉瘤则是从肿瘤这种相对更自然产生的扰乱后3D基因组结构中发现素材,验证拓扑结构域能在染色质重组后产生,并对细胞产生新的基因表达调控功能。这一工作更多的是为基因组结构研究以及肿瘤研究提供新的视角。

Abstract

Background: The organisation of vertebrate genomes into topologically associating domains(TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts.

Results: We show that interactions within the PAX3 and FOXO1 domains are restricted to their respective TADs in normal conditions, while in apatient-derived alveolar rhabdomyosarcoma cell line, harbouring the diagnostict(2;13)(q35;q14) translocation that brings together the PAX3 and FOXO1 genes,the PAX3 promoter interacts ectopically with FOXO1 sequences.Using a combination of 4C-seq datasets, we have modelled the three-dimensiona lorganisation of the fused landscape in alveolar rhabdomyosarcoma.

Conclusions:The chromosomal translocation that leads to alveolar rhabdomyosarcoma development generates a novel TAD that is likely to favour ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories. Rhabdomyosarcomas may therefore arise from cells which do not normally express PAX3. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs,respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions. Our results demonstrate that, upon translocation, novel regulatory landscapes are formed allowing new intra-TAD interactions between the original loci involved.

 

文章二

Lineage-specific rediploidization is a mechanism to explain time-lags between genome duplication and evolutionary diversification

鲑鱼系演化历史研究:基因组翻倍再重新两倍化

Fiona M.Robertson, Manu Kumar Gundappa, Fabian Grammes, Torgeir R. Hvidsten, Anthony K.Redmond, Sigbjørn Lien, Samuel A. M. Martin, Peter W. H. Holland, Simen R.Sandve and Daniel J. Macqueen

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1241-z

【导读】在物种演化过程中基因组翻倍并不是一个罕见现象,基因组翻倍往往能产生新的物种去适应不同的环境。鲑鱼的祖先就发生过这样的情况,然后又经历了重新二倍体化的演化过程,本周的这一工作为我们分析了这一演化过程中基因组发生的变化。

Abstract

Background:The functional divergence of duplicate genes (ohnologues) retained from whole genome duplication (WGD) is thought to promote evolutionary diversification. However, species radiation and phenotypic diversification are often temporally separated from WGD. Salmonid fish, whose ancestor underwent WGD by autotetraploidization ~95 million years ago, fit such a ‘time-lag’ model of post-WGD radiation, which occurred alongside a major delay in the rediploidization process. Here we propose a model, ‘lineage-specific ohnologue resolution’ (LORe), to address the consequences of delayed rediploidization.Under LORe, speciation precedes rediploidization, allowing independent ohnologue divergence in sister lineages sharing an ancestral WGD event.

Results:Using cross-species sequence capture, phylogenomics and genome-wide analyses of ohnologue expression divergence, we demonstrate the major impact of LORe on salmonid evolution. One-quarter of each salmonid genome, harbouring at least 4550 ohnologues, has evolved under LORe, with rediploidization and functional divergence occurring on multiple independent occasions >50 million years post-WGD. We demonstrate the existence and regulatory divergence of many LORe ohnologues with functions in lineage-specific physiological adaptations that potentially facilitated salmonid species radiation. We show that LORe ohnologues are enriched for different functions than ‘older’ ohnologues that began diverging in the salmonid ancestor.

Conclusions:LORe has unappreciated significance as a nested component of post-WGD divergence that impacts the functional properties of genes, whilst providing ohnologues available solely for lineage-specificad aptation. Under LORe, which is predicted following many WGD events, the functional outcomes of WGD need not appear ‘explosively’, but can arise gradually over tens of millions of years, promoting lineage-specific diversification regimes under prevailing ecological pressures.

 

文章三

“Like sugar in milk”: reconstructing the genetic history of the Parsi population

印度帕西人的“水乳交融”遗传演化史

Gyaneshwer Chaubey, Qasim Ayub, Niraj Rai, Satya Prakash, Veena Mushrif-Tripathy, Massimo Mezzavilla, Ajai Kumar Pathak, Rakesh Tamang, Sadaf Firasat, Maere Reidla,Monika Karmin, Deepa Selvi Rani, Alla G. Reddy, Jüri Parik, Ene Metspalu, Siiri Rootsi, Kurush Dalal, Shagufta Khaliq, Syed Qasim Mehdi^, Lalji Singh,Mait Metspalu, Toomas Kivisild, Chris Tyler-Smith,  Richard Villems† and  Kumarasamy Thangaraj

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1244-9

【导读】波斯古国在公元8-10世纪伊斯兰大征服期间渐渐灭亡,原波斯人逃亡至印度,被当时的印度国王收留,奉旨文化融和“水乳交融”(like sugar in milk),成为印度帕西民族。至2011年印度人口普查,这一民族已不足6万人口。2013年印度政府开展维持帕西人口数量工作,提出“帕西万寿无疆”(“Jiyo Parsi”-long live Parsi)。本周这一工作从帕西族以及周边印度其他族裔的DNA出发,为我们演示几个世纪的民族迁徙和演化如何在我们的遗传物质上留下印记。

Abstract

Background:The chromodomain helicase DNA-binding family of ATP-dependent chromatin remodeling factors play essential roles during eukaryote growth and development. They are recruited by specific transcription factors and regulate the expression of developmentally important genes. Here, we describe an unexpected role in non-coding RNA-directed DNA methylation in Arabidopsis thaliana.

Results:Through forward genetic screens we identified PKL, a gene required for developmental regulation inplants, as a factor promoting transcriptional silencing at the transgenic RD29A promoter.Mutation of PKL results in DNA methylation changes at more than half of the loci that are targeted by RNA-directed DNA methylation (RdDM).A small number of transposable elements and genes had reduced DNA methylation correlated with derepression in the pkl mutant, though for the majority, decreases in DNA methylation are not sufficient to cause release of silencing. The changes in DNA methylation in the pkl mutantare positively correlated with changes in 24-nt siRNA levels. In addition, PKL is required for the accumulation of PolV-dependent transcripts and for the positioning of Pol V-stabilized nucleosomes at several tested loci, indicating that RNA polymerase V-related functions are impaired in the pkl mutant.

Conclusions:PKL is required for transcriptional silencing and has significant effects on RdDM in plants. The changes in DNA methylation in the pkl mutant are correlated with changes in the non-coding RNAs produced by Pol IV and Pol V. We propose that at RdDM target regions, PKL may be required to create a chromatin environment that influences non-coding RNA production, DNA methylation, and transcriptional silencing.

 

文章四

Differentiated demographic histories and local adaptations between Sherpas and Tibetans

夏尔巴人的演化历史和高原适应

Chao Zhang, Yan Lu, Qidi Feng, Xiaoji Wang, Haiyi Lou, Jiaojiao Liu, Zhilin Ning, Kai Yuan,Yuchen Wang, Ying Zhou, Lian Deng, Lijun Liu, Yajun Yang, Shilin Li, Lifeng Ma,Zhiying Zhang,Li Jin,Bing Su,Longli Kang and Shuhua Xu

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1242-y

【导读】另一个非常独特的少数民族族群是生活在喜马拉雅高原上的夏尔巴人,6月16日BioMedCentral开放获取出版官方微信的头条为我们更详细地介绍了这一工作。

Abstract

Background:The genetic relationships reported by recent studies between Sherpas and Tibetans are controversial. To gain insights into the population history and the genetic basis of high-altitude adaptation of the two groups, we analyzed genome-wide data in 111 Sherpas (Tibet and Nepal) and 177 Tibetans (Tibet and Qinghai),together with available data from present-day human populations.

Results:Sherpas and Tibetans show considerable genetic differences and can be distinguished as two distinct groups, even though the divergence between them(~3200–11,300 years ago) is much later than that between Han Chinese and either of the two groups (~6200–16,000 years ago). Sub-population structures exist in both Sherpas and Tibetans, corresponding to geographical or linguistic groups. Differentiation of genetic variants between Sherpas and Tibetans associated with adaptation to either high-altitude or ultraviolet radiation were identified and validated by genotyping additional Sherpa and Tibetan samples.

Conclusions:Our analyses indicate that both Sherpas and Tibetans are admixed populations, but the findings do not support the previous hypothesis that Tibetans derive their ancestry from Sherpas and Han Chinese. Compared to Tibetans, Sherpas show higher levels of South Asian ancestry, while Tibetans show higher levels of East Asian and Central Asian/Siberian ancestry. We propose a new model to elucidate the differentiated demographic histories and local adaptations of Sherpas and Tibetans.

 

文章五

CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion

CRISPR/Cas9引起的外显子剪切现象

Haiwei Mou,Jordan L. Smith, Lingtao Peng, Hao Yin, Jill Moore, Xiao-Ou Zhang, Chun-Qing Song, Ankur Sheel, Qiongqiong Wu, Deniz M. Ozata, Yingxiang Li, Daniel G.Anderson, Charles P. Emerson, Erik J. Sontheimer, Melissa J. Moore, Zhiping Weng, Xue Wen

http://genomebiology.biomedcentral.com/articles/10.1186/s13059-017-1237-8

【导读】近日Nature Methods 上发表的大规模CRISPR/Cas9脱靶效应研究引起了科研圈的热议,在这一篇众说纷纭之中,Genome Biology本周发表的这一工作发现的是少数一些先导RNA引起的基因外显子缺失的“外显子跳跃”现象。欢迎热心读者重复验证这些发现。

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