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转录核心抑制因子 CTBP-1 与 SOX 家族转录因子 EGL-13 一起作用,维持 中的 AIA 中间神经元细胞特性。

The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in .

机构信息

Department of Biology, Massachusetts Institute of Technology, Howard Hughes Medical Institute, Cambridge, United States.

出版信息

Elife. 2022 Feb 4;11:e74557. doi: 10.7554/eLife.74557.

Abstract

Cell identity is characterized by a distinct combination of gene expression, cell morphology, and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here, we show that the gene which encodes the transcriptional corepressor erminal inding rotein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in later larval stage and adult worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the mutant phenotype, we identified the gene which encodes a SOX family transcription factor. We found that regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

摘要

细胞身份特征在于特定的基因表达、细胞形态和细胞功能的组合,这些特征在祖细胞分裂和分化后建立。建立后,细胞身份可能不稳定,需要在细胞的剩余生命中积极和持续地维持。维持细胞身份的机制尚未完全了解。在这里,我们表明,编码转录核心抑制因子末端结合蛋白-1(CTBP-1)的基因对于线虫中两个 AIA 中间神经元身份的维持是必不可少的,CTBP-1 不是 AIA 细胞命运建立所必需的,而是自主发挥作用,可以在后期幼虫阶段和成虫中维持适当的 AIA 基因表达、形态和功能。从筛选 突变表型的抑制子中,我们鉴定了编码 SOX 家族转录因子的基因 。我们发现 调节 AIA 的功能和 AIA 基因表达的某些方面,但不调节 AIA 形态。我们得出结论,CTBP-1 蛋白通过利用 EGL-13 来抑制 AIAs 中的转录活性,部分维持 AIA 细胞身份。更普遍地说,我们提出像 CTBP-1 这样的转录核心抑制因子可能是维持细胞身份的关键因素,利用 EGL-13 等转录因子的 DNA 结合特异性以细胞特异性方式选择性地调节基因表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6722/8816384/353d9510db94/elife-74557-fig1.jpg

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