TALE factors use two distinct functional modes to control an essential zebrafish gene expression program

  1. Franck Ladam
  2. William Stanney
  3. Ian J Donaldson
  4. Ozge Yildiz
  5. Nicoletta Bobola
  6. Charles G Sagerström  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. University of Manchester, United Kingdom

Abstract

TALE factors are broadly expressed embryonically and known to function in complexes with transcription factors (TFs) like Hox proteins at gastrula/segmentation stages, but it is unclear if such generally expressed factors act by the same mechanism throughout embryogenesis. We identify a TALE-dependent gene regulatory network (GRN) required for anterior development and detect TALE occupancy associated with this GRN throughout embryogenesis. At blastula stages, we uncover a novel functional mode for TALE factors, where they occupy genomic DECA motifs with nearby NF-Y sites. We demonstrate that TALE and NF-Y form complexes and regulate chromatin state at genes of this GRN. At segmentation stages, GRN-associated TALE occupancy expands to include HEXA motifs near PBX:HOX sites. Hence, TALE factors control a key GRN, but utilize distinct DNA motifs and protein partners at different stages - a strategy that may also explain their oncogenic potential and may be employed by other broadly expressed TFs.

Data availability

RNA-seq data has been deposited in GEO under accession code GSE102662ChIP-seq data has been deposited in ArrayExpress under accession code E-MTAB-5967

The following data sets were generated
    1. Ladam F
    2. Sagerstrom CG
    (2018) Zebrafish TALE KD RNA-seq
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE102662).
The following previously published data sets were used
    1. Hans-Jörg Warnatz
    (2015) Prep1 (ChIP-Seq)
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1545025).
    1. Ozren Bogdanovic
    (2012) H3K4me1_dome, danRer7
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915193).
    1. Ozren Bogdanovic
    (2012) H3K4me3_dome, danRer7
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915189).
    1. Ozren Bogdanovic
    (2012) H3K27ac_dome, danRer7
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915197.
    1. Ozren Bogdanovic
    (2012) H3K27ac_80%epi, danRer7
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915198).
    1. Ozren Bogdanovic
    (2012) H3K27ac_24hpf, danRer7
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915199).
    1. Yong Zhang
    (2013) H3K27me3 ChIP-seq dome
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081557).
    1. Yong Zhang
    (2013) nucleosome dome rep 1
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081554).
    1. Yong Zhang
    (2013) Pol II ChIP-seq dome 8WG16
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081560).
    1. Hyung Joo Lee
    (2015) MeDIP_4.5hpf
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1274386).
    1. Raja Jothi
    (2014) ChIP-Seq NF-YA
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1370111).
    1. ENCODE DCC
    (2012) LICR_ChipSeq_ES-E14_H3K4me1_E0
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000121).
    1. ENCODE DCC
    (2012) LICR_ChipSeq_ES-E14_H3K4me3_E0
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000124).
    1. ENCODE DCC
    (2012) LICR_ChipSeq_ES-E14_H3K27ac_E0
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000126).
    1. ENCODE DCC
    (2012) LICR_ChipSeq_ES-Bruce4_H3K27me3_E
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000089).
    1. ENCODE DCC
    (2012) UW_DnaseSeq_ES-E14_E0_129/Ola
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1014154).
    1. Chieh-Chun Chen
    (2014) E14 MeDIP-seq
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM859494).
    1. Hans-Jörg Warnatz
    (2015) Input_DNA (ChIP-Seq control)
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1545026).

Article and author information

Author details

  1. Franck Ladam

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. William Stanney

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ian J Donaldson

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Ozge Yildiz

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nicoletta Bobola

    Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7103-4932
  6. Charles G Sagerström

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Charles.Sagerstrom@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1509-5810

Funding

National Institute of Neurological Disorders and Stroke (NS38183)

  • Charles G Sagerström

Biotechnology and Biological Sciences Research Council (BB/N00907X/1)

  • Nicoletta Bobola

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was submitted to and approved by the University of Massachusetts Medical School Institutional Animal Care and Use Committee (protocol A-1565) and the University of Massachusetts Medical School Institutional Review Board (protocol I-149).

Copyright

© 2018, Ladam 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.

Metrics

  • 1,566
    views
  • 173
    downloads
  • 24
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Franck Ladam
  2. William Stanney
  3. Ian J Donaldson
  4. Ozge Yildiz
  5. Nicoletta Bobola
  6. Charles G Sagerström
(2018)
TALE factors use two distinct functional modes to control an essential zebrafish gene expression program
eLife 7:e36144.
https://doi.org/10.7554/eLife.36144

Share this article

https://doi.org/10.7554/eLife.36144

Further reading

    1. Developmental Biology
    Bin Zhu, Rui Wei ... Pei Liang
    Research Article

    Wing dimorphism is a common phenomenon that plays key roles in the environmental adaptation of aphid; however, the signal transduction in response to environmental cues and the regulation mechanism related to this event remain unknown. Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification that extends transcriptome variety without altering the genome, playing essential roles in numerous biological and physiological processes. Here, we present a chromosome-level genome assembly of the rose-grain aphid Metopolophium dirhodum by using PacBio long HiFi reads and Hi-C technology. The final genome assembly for M. dirhodum is 447.8 Mb, with 98.50% of the assembled sequences anchored to nine chromosomes. The contig and scaffold N50 values are 7.82 and 37.54 Mb, respectively. A total of 18,003 protein-coding genes were predicted, of which 92.05% were functionally annotated. In addition, 11,678 A-to-I RNA-editing sites were systematically identified based on this assembled M. dirhodum genome, and two synonymous A-to-I RNA-editing sites on CYP18A1 were closely associated with transgenerational wing dimorphism induced by crowding. One of these A-to-I RNA-editing sites may prevent the binding of miR-3036-5p to CYP18A1, thus elevating CYP18A1 expression, decreasing 20E titer, and finally regulating the wing dimorphism of offspring. Meanwhile, crowding can also inhibit miR-3036-5p expression and further increase CYP18A1 abundance, resulting in winged offspring. These findings support that A-to-I RNA editing is a dynamic mechanism in the regulation of transgenerational wing dimorphism in aphids and would advance our understanding of the roles of RNA editing in environmental adaptability and phenotypic plasticity.

    1. Developmental Biology
    Hanee Lee, Junsu Kang ... Junho Lee
    Research Article

    The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature deformation of touch neurons and impaired touch responses in a yap-1/YAP-dependent manner, the downstream transcriptional co-activator of LATS. Decreased movement as well as microtubule destabilization by treatment with colchicine or disruption of microtubule-stabilizing genes alleviated the neuronal deformation of wts-1 mutants. Colchicine exerted neuroprotective effects even during normal aging. In addition, the deficiency of a microtubule-severing enzyme spas-1 also led to precocious structural deformation. These results consistently suggest that hyper-stabilized microtubules in both wts-1-deficient neurons and normally aged neurons are detrimental to the maintenance of neuronal structural integrity. In summary, Hpo pathway governs the structural and functional maintenance of differentiated neurons by modulating microtubule stability, raising the possibility that the microtubule stability of fully developed neurons could be a promising target to delay neuronal aging. Our study provides potential therapeutic approaches to combat age- or disease-related neurodegeneration.