Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila.
Motif 1 Binding Protein suppresses wingless to promote eye fate in Drosophila.
复制标题
基序1结合蛋白抑制果蝇无翅，促进眼睛的命运。
DOI：
10.1038/s41598-020-73891-7
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发表时间：
2020-10-14
影响因子：
4.6
通讯作者：
Singh A
中科院分区：
文献类型：
--
作者：
Raj A;Chimata AV;Singh A
RNA聚合酶II(Pol II)在转录起始点(TSS)的暂停现象是调控全基因组基因表达的关键限速步骤之一。在果蝇胚胎中，Pol II停顿被认为可以调节发育控制基因的表达，然而，Pol II停顿在发育后期的时间窗中的功能意义仍不清楚。一个高度保守的锌指转录因子，基序1结合蛋白(M1BP)，被认为是协调启动子-近端暂停。我们发现了M1BP在调节果蝇眼睛发育中的新作用。M1BP功能的下调抑制了眼睛的命运，导致眼睛明显减少或表现为“无眼”。M1BP的眼睛抑制功能在发育的眼睛中没有结构域限制。M1BP的下调导致了无翼(WG)基因表达的两倍以上的诱导，同时也导致了对眼睛命运的负面调节-同胸(HTH)的强烈诱导。M1BP下调的失明表型依赖于Wg的上调，因为通过使用wgRNAi下调M1BP和WG，显示出明显的眼睛减退或“无眼”表型，这伴随着眼睛想象盘中WG和hth表达水平的正常化。Wg的异位诱导被认为会引发发育中的细胞死亡。我们发现，由于M1BP下调而导致的WG上调也会诱导细胞凋亡，通过阻断caspase介导的细胞死亡可以显著恢复这一过程。我们的数据有力地表明POL II暂停因子M1BP对WG的转录调控可能是果蝇眼睛发育过程中的重要调控机制之一(S)。
The phenomenon of RNA polymerase II (Pol II) pausing at transcription start site (TSS) is one of the key rate-limiting steps in regulating genome-wide gene expression. In Drosophila embryo, Pol II pausing is known to regulate the developmental control genes expression, however, the functional implication of Pol II pausing during later developmental time windows remains largely unknown. A highly conserved zinc finger transcription factor, Motif 1 Binding Protein (M1BP), is known to orchestrate promoter-proximal pausing. We found a new role of M1BP in regulating Drosophila eye development. Downregulation of M1BP function suppresses eye fate resulting in a reduced eye or a “no-eye” phenotype. The eye suppression function of M1BP has no domain constraint in the developing eye. Downregulation of M1BP results in more than two-fold induction of wingless (wg) gene expression along with robust induction of Homothorax (Hth), a negative regulator of eye fate. The loss-of-eye phenotype of M1BP downregulation is dependent on Wg upregulation as downregulation of both M1BP and wg, by using wgRNAi, shows a significant rescue of a reduced eye or a “no-eye” phenotype, which is accompanied by normalizing of wg and hth expression levels in the eye imaginal disc. Ectopic induction of Wg is known to trigger developmental cell death. We found that upregulation of wg as a result of downregulation of M1BP also induces apoptotic cell death, which can be significantly restored by blocking caspase-mediated cell death. Our data strongly imply that transcriptional regulation of wg by Pol II pausing factor M1BP may be one of the important regulatory mechanism(s) during Drosophila eye development.
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影响因子：
5.3
作者：
GILMOUR, DS;LIS, JT
通讯作者：
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