Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning.
Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning.
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DOI：
10.1371/journal.pgen.1003753
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Mann RS
中科院分区：
文献类型：
--
作者：
Slattery M;Voutev R;Ma L;Nègre N;White KP;Mann RS
The Yorkie/Yap transcriptional coactivator is a well-known regulator of cellular proliferation in both invertebrates and mammals. As a coactivator, Yorkie (Yki) lacks a DNA binding domain and must partner with sequence-specific DNA binding proteins in the nucleus to regulate gene expression; in Drosophila, the developmental regulators Scalloped (Sd) and Homothorax (Hth) are two such partners. To determine the range of target genes regulated by these three transcription factors, we performed genome-wide chromatin immunoprecipitation experiments for each factor in both the wing and eye-antenna imaginal discs. Strong, tissue-specific binding patterns are observed for Sd and Hth, while Yki binding is remarkably similar across both tissues. Binding events common to the eye and wing are also present for Sd and Hth; these are associated with genes regulating cell proliferation and “housekeeping” functions, and account for the majority of Yki binding. In contrast, tissue-specific binding events for Sd and Hth significantly overlap enhancers that are active in the given tissue, are enriched in Sd and Hth DNA binding sites, respectively, and are associated with genes that are consistent with each factor's previously established tissue-specific functions. Tissue-specific binding events are also significantly associated with Polycomb targeted chromatin domains. To provide mechanistic insights into tissue-specific regulation, we identify and characterize eye and wing enhancers of the Yki-targeted bantam microRNA gene and demonstrate that they are dependent on direct binding by Hth and Sd, respectively. Overall these results suggest that both Sd and Hth use distinct strategies – one shared between tissues and associated with Yki, the other tissue-specific, generally Yki-independent and associated with developmental patterning – to regulate distinct gene sets during development. The Hippo tumor suppressor pathway controls proliferation in a tissue-nonspecific fashion in Drosophila epithelial progenitor tissues via the transcriptional coactivator Yorkie (Yki). However, despite the tissue-nonspecific role that Yki plays in tissue growth, the transcription factors that recruit Yki to DNA, most notably Scalloped (Sd) and Homothorax (Hth), are important regulators of developmental patterning with many tissue-specific functions. Thus, these three transcriptional regulators – Yki, Sd, and Hth – provide a model for exploring the properties of protein-DNA interactions that regulate both tissue-shared and tissue-specific functions. With this goal in mind, we identified the positions in the fly genome that are bound by Yki, Sd, and Hth in the progenitors of the wing and eye-antenna structures of the fly. These data not only provide a global view of the Yki gene regulatory network, they reveal an unusual amount of tissue specificity in the genomic regions targeted by Sd and Hth, but not Yki. The data also reveal that tissue-specific binding is very likely to overlap tissue-specific enhancer regions, provide important clues for how tissue-specific Sd and Hth binding occurs, and support the idea that gene regulatory networks are plastic, with spatial differences in binding significantly impacting network structures.
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影响因子：
10.5
作者：
Bessa, J;Gebelein, B;Mann, RS
通讯作者：
Mann, RS
影响因子：
4
作者：
Barolo, Scott
通讯作者：
Barolo, Scott
影响因子：
64.5
作者：
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通讯作者：
SHENK, T
影响因子：
8.8
作者：
Gaertner B;Johnston J;Chen K;Wallaschek N;Paulson A;Garruss AS;Gaudenz K;De Kumar B;Krumlauf R;Zeitlinger J
通讯作者：
Zeitlinger J
影响因子：
12.3
作者：
Frietze S;Wang R;Yao L;Tak YG;Ye Z;Gaddis M;Witt H;Farnham PJ;Jin VX
通讯作者：
Jin VX