The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development

Summary SMRTER (SMRT-related and ecdysone receptor interacting factor) is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicat...

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Main Authors: Bryan W. Heck, Bin Zhang, Xin Tong, Zui Pan, Wu-Min Deng, Chih-Cheng Tsai
Format: Article
Language:English
Published: The Company of Biologists 2011-12-01
Series:Biology Open
Subjects:
Online Access:http://bio.biologists.org/content/1/3/182
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author Bryan W. Heck
Bin Zhang
Xin Tong
Zui Pan
Wu-Min Deng
Chih-Cheng Tsai
author_facet Bryan W. Heck
Bin Zhang
Xin Tong
Zui Pan
Wu-Min Deng
Chih-Cheng Tsai
author_sort Bryan W. Heck
collection DOAJ
description Summary SMRTER (SMRT-related and ecdysone receptor interacting factor) is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicated them in a wide range of transcriptional regulatory pathways. However, little is currently known about how this conserved class of transcriptional corepressors regulates the development of particular tissues via specific pathways. In this study, through our characterization of multiple Smrter (Smr) mutant lines, mosaic analysis of a loss-of-function Smr allele, and studies of two independent Smr RNAi fly lines, we report that SMRTER is required for the development of both ovarian follicle cells and the wing. In these two tissues, SMRTER inhibits not only the ecdysone pathway, but also the Notch pathway. We differentiate SMRTER's influence on these two signaling pathways by showing that SMRTER inhibits the Notch pathway, but not the ecdysone pathway, in a spatiotemporally restricted manner. We further confirm the likely involvement of SMRTER in the Notch pathway by demonstrating a direct interaction between SMRTER and Suppressor of Hairless [Su(H)], a DNA-binding transcription factor pivotal in the Notch pathway, and the colocalization of both proteins at many chromosomal regions in salivary glands. Based on our results, we propose that SMRTER regulates the Notch pathway through its association with Su(H), and that overcoming a SMRTER-mediated transcriptional repression barrier may represent a key mechanism used by the Notch pathway to control the precise timing of events and the formation of sharp boundaries between cells in multiple tissues during development.
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spelling doaj.art-7794a932cafa4009a4e058dac8d0e78b2022-12-21T22:53:26ZengThe Company of BiologistsBiology Open2046-63902011-12-011318219610.1242/bio.20120472012047The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila developmentBryan W. Heck0Bin Zhang1Xin Tong2Zui Pan3Wu-Min Deng4Chih-Cheng Tsai5 UMDNJ-Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA UMDNJ-Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA UMDNJ-Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA UMDNJ-Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA UMDNJ-Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA Summary SMRTER (SMRT-related and ecdysone receptor interacting factor) is the Drosophila homologue of the vertebrate proteins SMRT and N-CoR, and forms with them a well-conserved family of transcriptional corepressors. Molecular characterization of SMRT-family proteins in cultured cells has implicated them in a wide range of transcriptional regulatory pathways. However, little is currently known about how this conserved class of transcriptional corepressors regulates the development of particular tissues via specific pathways. In this study, through our characterization of multiple Smrter (Smr) mutant lines, mosaic analysis of a loss-of-function Smr allele, and studies of two independent Smr RNAi fly lines, we report that SMRTER is required for the development of both ovarian follicle cells and the wing. In these two tissues, SMRTER inhibits not only the ecdysone pathway, but also the Notch pathway. We differentiate SMRTER's influence on these two signaling pathways by showing that SMRTER inhibits the Notch pathway, but not the ecdysone pathway, in a spatiotemporally restricted manner. We further confirm the likely involvement of SMRTER in the Notch pathway by demonstrating a direct interaction between SMRTER and Suppressor of Hairless [Su(H)], a DNA-binding transcription factor pivotal in the Notch pathway, and the colocalization of both proteins at many chromosomal regions in salivary glands. Based on our results, we propose that SMRTER regulates the Notch pathway through its association with Su(H), and that overcoming a SMRTER-mediated transcriptional repression barrier may represent a key mechanism used by the Notch pathway to control the precise timing of events and the formation of sharp boundaries between cells in multiple tissues during development.http://bio.biologists.org/content/1/3/182SMRTERNotchSu(H)EcdysoneEcROogenesis
spellingShingle Bryan W. Heck
Bin Zhang
Xin Tong
Zui Pan
Wu-Min Deng
Chih-Cheng Tsai
The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
Biology Open
SMRTER
Notch
Su(H)
Ecdysone
EcR
Oogenesis
title The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
title_full The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
title_fullStr The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
title_full_unstemmed The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
title_short The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development
title_sort transcriptional corepressor smrter influences both notch and ecdysone signaling during drosophila development
topic SMRTER
Notch
Su(H)
Ecdysone
EcR
Oogenesis
url http://bio.biologists.org/content/1/3/182
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