Dense Bicoid hubs accentuate binding along the morphogen gradient.
Dense Bicoid hubs accentuate binding along the morphogen gradient.
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DOI：
10.1101/gad.305078.117
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发表时间：
2017-09-01
影响因子：
10.5
通讯作者：
Darzacq X
中科院分区：
文献类型：
--
作者：
Mir M;Reimer A;Haines JE;Li XY;Stadler M;Garcia H;Eisen MB;Darzacq X
Mir等人使用点阵光片显微镜在早期果蝇胚胎中进行体内单分子成像，并观察到Bicoid形成局部高密度的短暂“枢纽”，随着因子水平下降，这些枢纽有助于结合。形态发生梯度指导发育胚胎的空间模式，然而，这些梯度的解释机制仍然难以捉摸。在这里，我们使用点阵光片显微镜进行体内单分子成像在早期果蝇胚胎的转录因子Bicoid，形成梯度，并启动图案沿着前后轴。与经典模型相反，我们观察到Bicoid在整个胚胎中以快速的解离速率结合DNA，使得其在靶位点的平均占有率是依赖于解离速率的。我们进一步观察到Bicoid形成局部高密度的瞬时“枢纽”，其随着因子水平下降而促进结合，包括在后部，尽管蛋白水平非常低，但我们观察到Bicoid结合。我们提出，通过聚类的转录因子对速率的局部调节提供了一种促进与低亲和力靶点结合的一般机制，这可能是其他发育转录因子的普遍特征。
Mir et al. used lattice light-sheet microscopy to perform in vivo single-molecule imaging in early Drosophila melanogaster embryos and observed Bicoid forming transient “hubs” of locally high density that facilitate binding as factor levels drop. Morphogen gradients direct the spatial patterning of developing embryos; however, the mechanisms by which these gradients are interpreted remain elusive. Here we used lattice light-sheet microscopy to perform in vivo single-molecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-rate-dependent. We further observed Bicoid forming transient “hubs” of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. We propose that localized modulation of transcription factor on rates via clustering provides a general mechanism to facilitate binding to low-affinity targets and that this may be a prevalent feature of other developmental transcription factors.
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影响因子：
9.8
作者：
Li XY;MacArthur S;Bourgon R;Nix D;Pollard DA;Iyer VN;Hechmer A;Simirenko L;Stapleton M;Luengo Hendriks CL;Chu HC;Ogawa N;Inwood W;Sementchenko V;Beaton A;Weiszmann R;Celniker SE;Knowles DW;Gingeras T;Speed TP;Eisen MB;Biggin MD
通讯作者：
Biggin MD
结合位点转换导致密切相关的果蝇物种之间的转录因子结合发生普遍的数量变化。
影响因子：
9.8
作者：
Bradley RK;Li XY;Trapnell C;Davidson S;Pachter L;Chu HC;Tonkin LA;Biggin MD;Eisen MB
通讯作者：
Eisen MB
影响因子：
9.2
作者：
Foo, Sun Melody;Sun, Yujia;Rushlow, Christine A.
通讯作者：
Rushlow, Christine A.
DOI：
10.1073/pnas.0506462102
发表时间：
2005-09-13
影响因子：
11.1
作者：
Lebrecht, D;Foehr, M;Hanes, SD
通讯作者：
Hanes, SD
影响因子：
64.5
作者：
DRIEVER, W;NUSSLEINVOLHARD, C
通讯作者：
NUSSLEINVOLHARD, C