1. Developmental Biology
  2. Chromosomes and Gene Expression
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The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation

  1. Anthony J Linares
  2. Chia-Ho Lin
  3. Andrey Damianov
  4. Katrina L Adams
  5. Bennett G Novitch
  6. Douglas L Black  Is a corresponding author
  1. University of California, Los Angeles, United States
Research Article
  • Cited 44
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Cite this article as: eLife 2015;4:e09268 doi: 10.7554/eLife.09268

Abstract

The RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, the role of the earlier PTBP1 program in embryonic stem cells (ESCs) and NPCs was not clear. We show that PTBP1 controls a program of neuronal gene expression that includes the transcription factor Pbx1. We identify exons specifically regulated by PTBP1 and not PTBP2 as mouse ESCs differentiate into NPCs. We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a isoform in ESCs. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of neuronal genes. Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program prior to induction of NPC development.

Article and author information

Author details

  1. Anthony J Linares

    Molecular Biology Institute Graduate Program, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  2. Chia-Ho Lin

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  3. Andrey Damianov

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  4. Katrina L Adams

    Molecular Biology Institute Graduate Program, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Bennett G Novitch

    Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  6. Douglas L Black

    Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    dougb@microbio.ucla.edu
    Competing interests
    Douglas L Black, Reviewing editor, eLife.

Reviewing Editor

  1. Benjamin J Blencowe, University of Toronto, Canada

Publication history

  1. Received: June 6, 2015
  2. Accepted: December 22, 2015
  3. Accepted Manuscript published: December 24, 2015 (version 1)
  4. Version of Record published: February 3, 2016 (version 2)
  5. Version of Record updated: April 27, 2016 (version 3)

Copyright

© 2015, Linares et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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