The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding.
The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding.
复制标题
DOI：
10.1186/gb-2011-12-4-r34
复制
发表时间：
2011
期刊：
影响因子：
12.3
通讯作者：
Biggin MD
中科院分区：
文献类型：
--
作者：
Li XY;Thomas S;Sabo PJ;Eisen MB;Stamatoyannopoulos JA;Biggin MD
在果蝇胚胎中，许多生物化学和功能无关的转录因子定量地结合到高度重叠的基因组区域，其中最低水平的结合是偶然的，DNA上的非功能性相互作用。驱动这些全基因组占据模式的主要生化机制尚未建立。在这里，我们使用从分离的胚胎细胞核的DNaseI消化的数据，以提供蛋白质可以访问基因组的不同区域的程度的生物物理测量。我们发现，在体内结合模式的21个发育调节定量相关的染色质中的DNA可及性。此外，我们发现，在体内的因子占用水平相关的程度更染色质的可及性比占用预测从体外亲和力测量使用纯化的蛋白质和裸DNA。然而，在可接近区域内，因子对DNA的固有亲和力在确定净占有率方面确实起作用，甚至弱亲和力识别位点也有贡献。最后，我们表明，程序化的变化，在不同的发展阶段之间的染色质可及性与定量改变因子结合。基于这些和其他结果，我们提出了一个一般的机制来解释广泛的，重叠的DNA结合动物转录因子。在这种观点中，转录因子在细胞中以足够高的浓度表达，使得它们可以在高度可接近的染色质中占据它们的识别序列，而无需与其他蛋白质的物理合作相互作用的帮助，从而导致不相关因子的高度重叠、分级结合。
In Drosophila embryos, many biochemically and functionally unrelated transcription factors bind quantitatively to highly overlapping sets of genomic regions, with much of the lowest levels of binding being incidental, non-functional interactions on DNA. The primary biochemical mechanisms that drive these genome-wide occupancy patterns have yet to be established. Here we use data resulting from the DNaseI digestion of isolated embryo nuclei to provide a biophysical measure of the degree to which proteins can access different regions of the genome. We show that the in vivo binding patterns of 21 developmental regulators are quantitatively correlated with DNA accessibility in chromatin. Furthermore, we find that levels of factor occupancy in vivo correlate much more with the degree of chromatin accessibility than with occupancy predicted from in vitro affinity measurements using purified protein and naked DNA. Within accessible regions, however, the intrinsic affinity of the factor for DNA does play a role in determining net occupancy, with even weak affinity recognition sites contributing. Finally, we show that programmed changes in chromatin accessibility between different developmental stages correlate with quantitative alterations in factor binding. Based on these and other results, we propose a general mechanism to explain the widespread, overlapping DNA binding by animal transcription factors. In this view, transcription factors are expressed at sufficiently high concentrations in cells such that they can occupy their recognition sequences in highly accessible chromatin without the aid of physical cooperative interactions with other proteins, leading to highly overlapping, graded binding of unrelated factors.
登录
查看更多内容
影响因子：
7
作者：
Bieda, M;Xu, XQ;Farnham, PJ
通讯作者：
Farnham, PJ
影响因子：
7.7
作者：
Boj SF;Servitja JM;Martin D;Rios M;Talianidis I;Guigo R;Ferrer J
通讯作者：
Ferrer J
影响因子：
12.3
作者：
Berman BP;Pfeiffer BD;Laverty TR;Salzberg SL;Rubin GM;Eisen MB;Celniker SE
通讯作者：
Celniker SE
影响因子：
11.4
作者：
Carr, A;Biggin, MD
通讯作者：
Biggin, MD
影响因子：
64.8
作者：
Clyde, DE;Corado, MSG;Small, S
通讯作者：
Small, S