Odd-paired is a pioneer-like factor that coordinates with Zelda to control gene expression in embryos
- California Institute of Technology, United States
- SUNY, United States
Abstract
Pioneer factors such as Zelda (Zld) help initiate zygotic transcription in Drosophila early embryos, but whether other factors support this dynamic process is unclear. Odd-paired (Opa), a zinc-finger transcription factor expressed at cellularization, controls the transition of genes from pair-rule to segmental patterns along the anterior-posterior axis. Finding that Opa also regulates expression through enhancer sog_Distal along the dorso-ventral axis, we hypothesized Opa’s role is more general. Chromatin-immunoprecipitation (ChIP-seq) confirmed its in vivo binding to sog_Distal but also identified widespread binding throughout the genome, comparable to Zld. Furthermore, chromatin assays (ATAC-seq) demonstrate that Opa, like Zld, influences chromatin accessibility genome-wide at cellularization, suggesting both are pioneer factors with common as well as distinct targets. Lastly, embryos lacking opa exhibit widespread, late patterning defects spanning both axes. Collectively, these data suggest Opa is a general timing factor and likely late-acting pioneer factor that drives a secondary wave of zygotic gene expression.
Data availability
GEO accession number SuperSeries GSE153329. SubSeries: ChIP-seq and singled-end ATAC-seq (GSE140722), and RNA-seq and paired-end ATAC-seq data access (GSE153328).RNA-seq and paired-end ATAC-seq data access: https://www.ncbi.nlm.nih.gov/geo/info/submissionftp.html, folder name: GEO_Theodora and Directory name: uploads/tkoromila_YTqdmKKoThe codes for RNA-seq, Opa ChIP-seq and ATAC-seq processing (alignment and peak calling) were uploaded to github: https://github.com/caltech-bioinformatics-resource-center/Stathopoulos_Lab
-
ChIP-seq and singled-end ATAC-seqNCBI Gene Expression Omnibus, GSE140722.
-
RNA-seq and paired-end ATAC-seq dataNCBI Gene Expression Omnibus, GSE153328.
Article and author information
Author details
Angelike Stathopoulos
Funding
National Institute of General Medical Sciences (R35GM118146)
- Angelike Stathopoulos
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD097535)
- Angelike Stathopoulos
Bioinformatics Resource Center at the Beckman Institute of Caltech (n/a)
- Fan Gao
Stony Brook University College of Arts and Sciences (n/a)
- J Peter Gergen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States
Version history
- Received: November 26, 2019
- Accepted: July 22, 2020
- Accepted Manuscript published: July 23, 2020 (version 1)
- Accepted Manuscript updated: July 24, 2020 (version 2)
- Version of Record published: August 10, 2020 (version 3)
Copyright
© 2020, Koromila 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
-
- 3,238
- views
-
- 364
- downloads
-
- 26
- 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)
Odd-paired is a pioneer-like factor that coordinates with Zelda to control gene expression in embryos
eLife 9:e59610.
https://doi.org/10.7554/eLife.59610
Further reading
-
- Developmental Biology
Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.
-
- Developmental Biology
- Structural Biology and Molecular Biophysics
The receptor tyrosine kinase ROR2 mediates noncanonical WNT5A signaling to orchestrate tissue morphogenetic processes, and dysfunction of the pathway causes Robinow syndrome, brachydactyly B, and metastatic diseases. The domain(s) and mechanisms required for ROR2 function, however, remain unclear. We solved the crystal structure of the extracellular cysteine-rich (CRD) and Kringle (Kr) domains of ROR2 and found that, unlike other CRDs, the ROR2 CRD lacks the signature hydrophobic pocket that binds lipids/lipid-modified proteins, such as WNTs, suggesting a novel mechanism of ligand reception. Functionally, we showed that the ROR2 CRD, but not other domains, is required and minimally sufficient to promote WNT5A signaling, and Robinow mutations in the CRD and the adjacent Kr impair ROR2 secretion and function. Moreover, using function-activating and -perturbing antibodies against the Frizzled (FZ) family of WNT receptors, we demonstrate the involvement of FZ in WNT5A-ROR signaling. Thus, ROR2 acts via its CRD to potentiate the function of a receptor super-complex that includes FZ to transduce WNT5A signals.
