title: Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Chaogu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Felix Qiaochu
authors.initials: FQ
authors.lastname: Jin
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: mc21@columbia.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Chalfie
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins