Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation

Cell differentiation usually occurs with high fidelity, but the expression of many transcription factors is variable. Using the touch receptor neurons (TRNs) in C. elegans, we found that the Hox proteins CEH-13/lab and EGL-5/Abd-B overcome this variability by facilitating the activation of the commo...

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Main Authors: Chaogu Zheng, Felix Qiaochu Jin, Martin Chalfie
Format: Article
Language:English
Published: Elsevier 2015-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715012140
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author Chaogu Zheng
Felix Qiaochu Jin
Martin Chalfie
author_facet Chaogu Zheng
Felix Qiaochu Jin
Martin Chalfie
author_sort Chaogu Zheng
collection DOAJ
description Cell differentiation usually occurs with high fidelity, but the expression of many transcription factors is variable. Using the touch receptor neurons (TRNs) in C. elegans, we found that the Hox proteins CEH-13/lab and EGL-5/Abd-B overcome this variability by facilitating the activation of the common TRN fate determinant mec-3 in the anterior and posterior TRNs, respectively. CEH-13 and EGL-5 increase the probability of mec-3 transcriptional activation by the POU-homeodomain transcription factor UNC-86 using the same Hox/Pbx binding site. Mutation of ceh-13 and egl-5 resulted in an incomplete (∼40%) loss of the TRN fate in respective TRNs, which correlates with quantitative mRNA measurements showing two distinct modes (all or none) of mec-3 transcription. Therefore, Hox proteins act as transcriptional “guarantors” in order to ensure reliable and robust gene expression during terminal neuronal differentiation. Guarantors do not activate gene expression by themselves but promote full activation of target genes regulated by other transcription factors.
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spelling doaj.art-c80218ccba2040bc9bfb0278ab45ddc72022-12-22T03:00:40ZengElsevierCell Reports2211-12472015-11-011371343135210.1016/j.celrep.2015.10.044Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal DifferentiationChaogu Zheng0Felix Qiaochu Jin1Martin Chalfie2Department of Biological Sciences, Columbia University, New York, NY 10027, USADepartment of Biological Sciences, Columbia University, New York, NY 10027, USADepartment of Biological Sciences, Columbia University, New York, NY 10027, USACell differentiation usually occurs with high fidelity, but the expression of many transcription factors is variable. Using the touch receptor neurons (TRNs) in C. elegans, we found that the Hox proteins CEH-13/lab and EGL-5/Abd-B overcome this variability by facilitating the activation of the common TRN fate determinant mec-3 in the anterior and posterior TRNs, respectively. CEH-13 and EGL-5 increase the probability of mec-3 transcriptional activation by the POU-homeodomain transcription factor UNC-86 using the same Hox/Pbx binding site. Mutation of ceh-13 and egl-5 resulted in an incomplete (∼40%) loss of the TRN fate in respective TRNs, which correlates with quantitative mRNA measurements showing two distinct modes (all or none) of mec-3 transcription. Therefore, Hox proteins act as transcriptional “guarantors” in order to ensure reliable and robust gene expression during terminal neuronal differentiation. Guarantors do not activate gene expression by themselves but promote full activation of target genes regulated by other transcription factors.http://www.sciencedirect.com/science/article/pii/S2211124715012140
spellingShingle Chaogu Zheng
Felix Qiaochu Jin
Martin Chalfie
Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
Cell Reports
title Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
title_full Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
title_fullStr Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
title_full_unstemmed Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
title_short Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation
title_sort hox proteins act as transcriptional guarantors to ensure terminal differentiation
url http://www.sciencedirect.com/science/article/pii/S2211124715012140
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AT felixqiaochujin hoxproteinsactastranscriptionalguarantorstoensureterminaldifferentiation
AT martinchalfie hoxproteinsactastranscriptionalguarantorstoensureterminaldifferentiation