TALE factors use two distinct functional modes to control an essential zebrafish gene expression program
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
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Zebrafish TALE KD RNA-seqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE102662).
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Prep1 (ChIP-Seq)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1545025).
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H3K4me1_dome, danRer7Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915193).
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H3K4me3_dome, danRer7Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915189).
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H3K27ac_dome, danRer7Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915197.
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H3K27ac_80%epi, danRer7Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915198).
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H3K27ac_24hpf, danRer7Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM915199).
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H3K27me3 ChIP-seq domePublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081557).
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nucleosome dome rep 1Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081554).
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Pol II ChIP-seq dome 8WG16Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1081560).
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MeDIP_4.5hpfPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1274386).
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ChIP-Seq NF-YAPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1370111).
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LICR_ChipSeq_ES-E14_H3K4me1_E0Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000121).
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LICR_ChipSeq_ES-E14_H3K4me3_E0Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000124).
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LICR_ChipSeq_ES-E14_H3K27ac_E0Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000126).
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LICR_ChipSeq_ES-Bruce4_H3K27me3_EPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1000089).
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UW_DnaseSeq_ES-E14_E0_129/OlaPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM1014154).
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E14 MeDIP-seqPublicly available at the NCBI Gene Expression Omnibus (accession no: GSM859494).
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Input_DNA (ChIP-Seq control)Publicly available at the NCBI Gene Expression Omnibus (accession no: GSM1545026).
Article and author information
Author details
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).
Reviewing Editor
- Marianne Bronner, California Institute of Technology, United States
Publication history
- Received: February 22, 2018
- Accepted: June 8, 2018
- Accepted Manuscript published: June 18, 2018 (version 1)
- Version of Record published: June 28, 2018 (version 2)
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.
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