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Publications (10 of 10) Show all publications
Dai, Q. (2023). Gene Regulation: Blocking the blocker. eLIFE, 12, Article ID e92076.
Open this publication in new window or tab >>Gene Regulation: Blocking the blocker
2023 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 12, article id e92076Article in journal (Refereed) Published
Abstract [en]

An unexpected interaction between a long non-coding RNA locus and a genetic insulator called Fub-1 has an important role in gene regulation during development in Drosophila. 

National Category
Genetics
Identifiers
urn:nbn:se:su:diva-234940 (URN)10.7554/eLife.92076 (DOI)001067120800001 ()37698172 (PubMedID)2-s2.0-85170631001 (Scopus ID)
Available from: 2024-10-30 Created: 2024-10-30 Last updated: 2024-10-30Bibliographically approved
He, L., Jones, J., He, W., Bjork, B. C., Wen, J. & Dai, Q. (2021). PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors. Development, 148(6), Article ID dev194670.
Open this publication in new window or tab >>PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
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2021 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 148, no 6, article id dev194670Article in journal (Refereed) Published
Abstract [en]

Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanismsthat drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.

Keywords
PRDM16, Radial glia, Temporal identity, Neocortex, Mouse
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-193398 (URN)10.1242/dev.194670 (DOI)000636462400011 ()33597191 (PubMedID)
Available from: 2021-05-25 Created: 2021-05-25 Last updated: 2023-04-04Bibliographically approved
Chui, A., Zhang, Q., Dai, Q. & Shi, S.-H. (2020). Oxidative stress regulates progenitor behavior and cortical neurogenesis. Development, 147(5), Article ID dev184150.
Open this publication in new window or tab >>Oxidative stress regulates progenitor behavior and cortical neurogenesis
2020 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 147, no 5, article id dev184150Article in journal (Refereed) Published
Abstract [en]

Orderly division of radial glial progenitors (RGPs) in the developing mammalian cerebral cortex generates deep and superficial layer neurons progressively. However, the mechanisms that control RGP behavior and precise neuronal output remain elusive. Here, we show that the oxidative stress level progressively increases in the developing mouse cortex and regulates RGP behavior and neurogenesis. As development proceeds, numerous gene pathways linked to reactive oxygen species (ROS) and oxidative stress exhibit drastic changes in RGPs. Selective removal of PRDM16, a transcriptional regulator highly expressed in RGPs, elevates ROS level and induces expression of oxidative stress- responsive genes. Coinciding with an enhanced level of oxidative stress, RGP behavior was altered, leading to abnormal deep and superficial layer neuron generation. Simultaneous expression of mitochondrially targeted catalase to reduce cellular ROS levels significantly suppresses cortical defects caused by PRDM16 removal. Together, these findings suggest that oxidative stress actively regulates RGP behavior to ensure proper neurogenesis in the mammalian cortex.

Keywords
Cortical development, Neocortical progenitor cells, Neurogenesis transition, Oxidative stress
National Category
Biological Sciences Neurosciences
Identifiers
urn:nbn:se:su:diva-181051 (URN)10.1242/dev.184150 (DOI)000522795200012 ()32041791 (PubMedID)
Available from: 2020-05-09 Created: 2020-05-09 Last updated: 2022-02-26Bibliographically approved
Rives-Quinto, N., Komori, H., Ostgaard, C. M., Janssens, D. H., Kondo, S., Dai, Q., . . . Lee, C.-Y. (2020). Sequential activation of transcriptional repressors promotes progenitor commitment by silencing stem cell identity genes. eLIFE, 9, Article ID e56187.
Open this publication in new window or tab >>Sequential activation of transcriptional repressors promotes progenitor commitment by silencing stem cell identity genes
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2020 (English)In: eLIFE, E-ISSN 2050-084X, Vol. 9, article id e56187Article in journal (Refereed) Published
Abstract [en]

Stem cells that indirectly generate differentiated cells through intermediate progenitors drives vertebrate brain evolution. Due to a lack of lineage information, how stem cell functionality, including the competency to generate intermediate progenitors, becomes extinguished during progenitor commitment remains unclear. Type II neuroblasts in fly larval brains divide asymmetrically to generate a neuroblast and a progeny that commits to an intermediate progenitor (INP) identity. We identified Tailless (Tll) as a master regulator of type II neuroblast functional identity, including the competency to generate INPs. Successive expression of transcriptional repressors functions through Hdac3 to silence tll during INP commitment. Reducing repressor activity allows re-activation of Notch in INPs to ectopically induce tll expression driving supernumerary neuroblast formation. Knocking-down hdac3 function prevents downregulation of tll during INP commitment. We propose that continual inactivation of stem cell identity genes allows intermediate progenitors to stably commit to generating diverse differentiated cells during indirect neurogenesis.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-189341 (URN)10.7554/eLife.56187 (DOI)000599508200001 ()33241994 (PubMedID)
Available from: 2021-01-21 Created: 2021-01-21 Last updated: 2022-02-25Bibliographically approved
Ueberschär, M., Wang, H., Zhang, C., Kondo, S., Aoki, T., Schedl, P., . . . Dai, Q. (2019). BEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila. Nature Communications, 10, Article ID 5700.
Open this publication in new window or tab >>BEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila
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2019 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 10, article id 5700Article in journal (Refereed) Published
Abstract [en]

The Drosophila genome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in transcriptional repression and chromatin insulation. A fourth protein-Elba3-bridges Elba1 and Elba2 to form an ELBA complex. Here, we report comprehensive investigation of these proteins in Drosophila embryos. We assess common and distinct binding sites for Insv and ELBA and their genetic interdependencies. While Elba1 and Elba2 binding generally requires the ELBA complex, Elba3 can associate with chromatin independently of Elba1 and Elba2. We further demonstrate that ELBA collaborates with other insulators to regulate developmental patterning. Finally, we find that adjacent gene pairs separated by an ELBA bound sequence become less differentially expressed in ELBA mutants. Transgenic reporters confirm the insulating activity of ELBA- and Insv-bound sites. These findings define ELBA and Insv as general insulator proteins in Drosophila and demonstrate the functional importance of insulators to partition transcription units.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-177447 (URN)10.1038/s41467-019-13558-8 (DOI)000502761400001 ()31836703 (PubMedID)
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2023-03-28Bibliographically approved
Strassman, A., Schnuetgen, F., Dai, Q., Jones, J. C., Gomez, A. C., Pitstick, L., . . . Bjork, B. C. (2017). Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping. Disease Models and Mechanisms, 10(7), 909-922
Open this publication in new window or tab >>Generation of a multipurpose Prdm16 mouse allele by targeted gene trapping
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2017 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 10, no 7, p. 909-922Article in journal (Refereed) Published
Abstract [en]

Gene trap mutagenesis is a powerful tool to create loss-of-function mutations in mice and other model organisms. Modifications of traditional gene trap cassettes, including addition of conditional features in the form of Flip-excision (FlEx) arrays to enable directional gene trap cassette inversions by Cre and Flpe site-specific recombinases, greatly enhanced their experimental potential. By taking advantage of these conditional gene trap cassettes, we developed a generic strategy for generating conditional mutations and validated this strategy in mice carrying a multipurpose allele of the Prdm16 transcription factor gene. We demonstrate that the gene trap insertion creates a null mutation replicating the Pierre Robin sequence-type cleft palate phenotype of other Prdm16 mutant mice. Consecutive breeding to Flpe and Emx1(IREScre) deleter mice spatially restricted Prdm16 loss to regions of the forebrain expressing the homeobox gene Emx1, demonstrating the utility of the technology for the analysis of tissue-specific gene functions.

Keywords
Conditional gene trap, Cleft palate, Mandible, Micrognathia, Pierre Robin sequence
National Category
Cell Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:su:diva-145334 (URN)10.1242/dmm.029561 (DOI)000404963600008 ()
Available from: 2017-07-28 Created: 2017-07-28 Last updated: 2022-03-23Bibliographically approved
Yao, L., Wang, S., Westholm, J. O., Dai, Q., Matsuda, R., Hosono, C., . . . Samakovlis, C. (2017). Genome-wide identification of Grainy head targets in Drosophila reveals regulatory interactions with the POU domain transcription factor Vvl. Development, 144(17), 3145-3155
Open this publication in new window or tab >>Genome-wide identification of Grainy head targets in Drosophila reveals regulatory interactions with the POU domain transcription factor Vvl
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2017 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 144, no 17, p. 3145-3155Article in journal (Refereed) Published
Abstract [en]

Grainy head (Grh) is a conserved transcription factor (TF) controlling epithelial differentiation and regeneration. To elucidate Grh functions we identified embryonic Grh targets by ChIP-seq and gene expression analysis. We show that Grh controls hundreds of target genes. Repression or activation correlates with the distance of Grh-binding sites to the transcription start sites of its targets. Analysis of 54 Grh-responsive enhancers during development and upon wounding suggests cooperation with distinct TFs in different contexts. In the airways, Grh-repressed genes encode key TFs involved in branching and cell differentiation. Reduction of the POU domain TF Ventral veins lacking (Vvl) largely ameliorates the airway morphogenesis defects of grh mutants. Vvl and Grh proteins additionally interact with each other and regulate a set of common enhancers during epithelial morphogenesis. We conclude that Grh and Vvl participate in a regulatory network controlling epithelial maturation.

Keywords
Drosophila, Airway, Chip-seq, Epithelial maturation, Grainy head, Microarray
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-147018 (URN)10.1242/dev.143297 (DOI)000408568500014 ()28760809 (PubMedID)
Available from: 2017-09-28 Created: 2017-09-28 Last updated: 2022-02-28Bibliographically approved
Ueberschär, M., Wen, J. & Dai, Q.BEN-solo proteins regulate genome accessibility.
Open this publication in new window or tab >>BEN-solo proteins regulate genome accessibility
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Active and silent transcriptional domains are established in parallel with the activation of the genome of a developing animal. Chromatin insulator elements separate transcription units and form barriers to limit the spread of different histone modifications. In contrast to other insulator binding proteins the BEN-solo proteins are expressed ubiquitously only at the stage of mid-blastula transition. They interact with other insulators and can partition the densely spaced transcription units in Drosophila ensuring their correct transcription, but their effect on chromatin architecture has never been explored. Here we show that the ELBA complex and Insv both regulate chromatin accessibility during genome activation. Many regions gain or lose signal in ATAC-seq in the mutants which is accompanied by changes in nascent transcription genome-wide. While ELBA contributes to the silencing of a reporter on the y chromosome, Insv appears to limit the spread of heterochromatin observed by the formation of HP1a-GFP foci. We conclude that ELBA and Insv act as chromatin barriers at a set of common target loci, but also diverge in their regulatory functions on heterochromatin, possibly via different interactors.

Keywords
BEN-solo, Elba, Insv, chromatin organization, genome accessibility, insulator, heterochromatin, barrier, mid-blastula transition
National Category
Cell Biology Genetics Developmental Biology
Research subject
Molecular Genetics; Molecular Biology; Developmental Biology
Identifiers
urn:nbn:se:su:diva-199708 (URN)
Available from: 2021-12-13 Created: 2021-12-13 Last updated: 2022-02-25
Yao, L., Wang, S., Dai, Q., Orzechowski-Westholm, J., Matsuda, R., Hosono, C., . . . Samakovlis, C.Genome-wide identification of Grainy head target genes in Drosophila reveals complex regulatory interactions between Grh and the POU-domain transcription factor, Vvl.
Open this publication in new window or tab >>Genome-wide identification of Grainy head target genes in Drosophila reveals complex regulatory interactions between Grh and the POU-domain transcription factor, Vvl
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(English)Manuscript (preprint) (Other academic)
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-129397 (URN)
Available from: 2016-04-21 Created: 2016-04-21 Last updated: 2022-02-23Bibliographically approved
Ueberschär, M., Wen, J. & Dai, Q.Insulator activity of paused promoters is independent of active transcription.
Open this publication in new window or tab >>Insulator activity of paused promoters is independent of active transcription
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Insulators are a class of cis-regulatory elements that organize genome architecture and separate transcription units. Recent evidence suggests that highly transcribed genes co-localize with insulators at chromatin boundaries. However, whether active transcription contributes to chromatin insulation remains unclear. In this study we address whether highly transcribed promoters, which are also in a paused state in the Drosophila embryo, function as insulators with the ability to block enhancer-promoter interaction. Using a transgenic reporter assay, we show that some, but not all, paused promoters act as insulators. To further dissect functional contribution of promoter pausing to enhancer-blocking activity, we focus on an insulator containing the paused wingless (wg) promoter, and find that depleting RNA polymerase II (Pol II) binding has no effect on its insulator function; instead, the insulator binding proteins GAF and ELBA as well as their cognate DNA motifs are essential. We therefore conclude that active transcription or Pol II pausing is not a general mechanism required for enhancer blocking and that the insulator activity is mainly conferred by insulator proteins.

Keywords
insulators, promoter pausing, transcription
National Category
Genetics Cell Biology Developmental Biology
Research subject
Molecular Biology; Molecular Genetics; Developmental Biology
Identifiers
urn:nbn:se:su:diva-199704 (URN)
Funder
Swedish Research Council, 2020-03543Swedish Cancer Society, CAN 20 1046 Pjf 01H
Available from: 2021-12-13 Created: 2021-12-13 Last updated: 2022-02-25
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-2082-0693

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