Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans.
Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans.
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DOI：
10.1186/1471-2164-11-465
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发表时间：
2010-08-06
期刊：
影响因子：
4.4
通讯作者：
Fire A
中科院分区：
文献类型：
--
作者：
Sha K;Gu SG;Pantalena-Filho LC;Goh A;Fleenor J;Blanchard D;Krishna C;Fire A
组织分化伴随着整个基因组基础染色质结构和动力学或表观基因组的变化。通过控制何时、何地以及哪些调节因子可以访问潜在的基因组DNA，表观基因组影响细胞的转录组，并最终影响其功能。现有的分析染色质特定细胞类型变化的基因组方法通常涉及两个元素：(I)不同类型的纯化细胞(或核)的来源，以及(Ii)通过活动或结构特征来分割或降解染色质的特定处理。对于许多令人感兴趣的细胞类型，这种分析受到我们无法在包含相互交织的其他细胞混合物的生物体或复杂组织中分离相关细胞群体的限制。这一限制将染色质动力学的现有知识限制在很小范围的生物系统(可以大量分选/分离/解剖的细胞类型和组织培养模型)或不同细胞类型的融合(组织块、整个生物体)。转基因驱动的DNA/染色质修饰酶的表达为查询表达定义的细胞亚群中的染色质结构提供了一个机会。在这项工作中，我们将细菌DNA腺嘌呤甲基转移酶(DAM)的体内表达与高通量测序相结合，在全基因组范围内采样组织特异性染色质的可及性。我们已经应用了这种方法(DALEC：直接不对称连接末端捕获)来绘制作为分化状态函数的基因组可及性的细胞类型特定视图。利用线虫菌株在不同组织(体壁肌肉、肠道和皮下组织)中表达DAM酶的优势，我们的努力产生了一个全基因组数据集，测量线虫(二倍体)基因组中538,000个DAM靶点的染色质可及性。验证DALEC作图结果，我们观察到核小体的观测覆盖率与大坝的低可及性之间存在很强的关联。值得注意的是，我们没有观察到任何被检查的组织的染色质的延伸区域。这些结果与“局部编排”模型一致，在该模型中，差异基因的表达是由染色质结构的复杂局部重排驱动的，而不是大染色体区域的总体不可穿透性。
Tissue differentiation is accompanied by genome-wide changes in the underlying chromatin structure and dynamics, or epigenome. By controlling when, where, and what regulatory factors have access to the underlying genomic DNA, the epigenome influences the cell's transcriptome and ultimately its function. Existing genomic methods for analyzing cell-type-specific changes in chromatin generally involve two elements: (i) a source for purified cells (or nuclei) of distinct types, and (ii) a specific treatment that partitions or degrades chromatin by activity or structural features. For many cell types of great interest, such assays are limited by our inability to isolate the relevant cell populations in an organism or complex tissue containing an intertwined mixture of other cells. This limitation has confined available knowledge of chromatin dynamics to a narrow range of biological systems (cell types that can be sorted/separated/dissected in large numbers and tissue culture models) or to amalgamations of diverse cell types (tissue chunks, whole organisms). Transgene-driven expression of DNA/chromatin modifying enzymes provides one opportunity to query chromatin structures in expression-defined cell subsets. In this work we combine in vivo expression of a bacterial DNA adenine methyltransferase (DAM) with high throughput sequencing to sample tissue-specific chromatin accessibility on a genome-wide scale. We have applied the method (DALEC: Direct Asymmetric Ligation End Capture) towards mapping a cell-type-specific view of genome accessibility as a function of differentiated state. Taking advantage of C. elegans strains expressing the DAM enzyme in diverse tissues (body wall muscle, gut, and hypodermis), our efforts yield a genome-wide dataset measuring chromatin accessibility at each of 538,000 DAM target sites in the C. elegans (diploid) genome. Validating the DALEC mapping results, we observe a strong association between observed coverage by nucleosomes and low DAM accessibility. Strikingly, we observed no extended regions of inaccessible chromatin for any of the tissues examined. These results are consistent with "local choreography" models in which differential gene expression is driven by intricate local rearrangements of chromatin structure rather than gross impenetrability of large chromosomal regions.
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影响因子：
10.5
作者：
KYRION, G;LIU, K;LUSTIG, AJ
通讯作者：
LUSTIG, AJ
DOI：
10.1073/pnas.91.4.1361
发表时间：
1994-02-15
影响因子：
11.1
作者：
KLADDE, MP;SIMPSON, RT
通讯作者：
SIMPSON, RT
DOI：
10.1101/sqb.2003.68.159
发表时间：
2003-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
McKay, SJ;Johnsen, R;Moerman, DG
通讯作者：
Moerman, DG
影响因子：
9.8
作者：
Hunt-Newbury R;Viveiros R;Johnsen R;Mah A;Anastas D;Fang L;Halfnight E;Lee D;Lin J;Lorch A;McKay S;Okada HM;Pan J;Schulz AK;Tu D;Wong K;Zhao Z;Alexeyenko A;Burglin T;Sonnhammer E;Schnabel R;Jones SJ;Marra MA;Baillie DL;Moerman DG
通讯作者：
Moerman DG
影响因子：
1.5
作者：
Bulanenkova, Svetlana;Snezhkov, Eugene;Sverdlov, Eugene
通讯作者：
Sverdlov, Eugene