Identification of novel retinoic acid target genes

Savory, Joanne G.A.; Edey, Caitlin; Hess, Bradley; Mears, Alan J.; Lohnes, David

doi:10.1016/j.ydbio.2014.09.013

Cited by 23 publications

(20 citation statements)

References 83 publications

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“…We have previously characterized the solution structures of the RXRA ΔAB-RARA ΔAB and RXRΔAB–RARA ΔABF complexes with the Rarb2 DR5 ( 60 ) and have shown that the presence of the RARA F domain leads to an increase in structural parameters indicating an extended non-interacting F domain. We now have selected another DR5 element from the F11r gene ( Supplementary Figure S1 ) which has been identified as a regulated RARE ( 13 , 61 ) and which exhibits similar binding as the Rarb2 DR5 ( 56 ) and Hoxb13 DR0 for which the polarity is defined as unique. The use of the coupled SEC-SAXS-TDA and the measurement of their subsequent SAXS intensity profiles (measured as I ( s ) versus s , where s = 4πsin θ /λ, 2 θ is the scattering angle) and the validation of the corresponding molecular weights (MWs) from the TDA that were compared to the MWs obtained directly from the SAXS data ( Supplementary Figure S6 ).…”

Section: Resultsmentioning

confidence: 99%

Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR

Ősz

McEwen

Bourguet

et al. 2020

Nucleic Acids Research

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Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR–RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR–RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR–RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR–RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR–RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR–RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR–RAR heterodimers.

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Section: Resultsmentioning

confidence: 99%

Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR

Ősz

McEwen

Bourguet

et al. 2020

Nucleic Acids Research

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“…34 In our data we found that the Ccnb1 mRNA was downregulated from the pre-leptotene stage, which suggests that Ccnb1 is dispensable for the meiocytes' chromatin remodeling. In addition, the Ccnd1 targeted by RA is highly expressed in the pre-leptotene cluster, 25 which suggests that it may be involved in the regulation of meiosis initiation.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals the landscape of early female germ cell development

Zhao

Meng

et al. 2020

FASEB j.

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Meiosis initiation is a crucial step for the production of haploid gametes, which occurs from anterior to posterior in fetal ovaries. The asynchrony of the transition from mitosis to meiosis results in heterogeneity in the female germ cell populations, which limits the studies of meiosis initiation and progression at a higher resolution level. To dissect the process of meiosis initiation, we investigated the transcriptional profiles of 19 363 single germ cells collected from E12.5, E14.5, and E16.5 mouse fetal ovaries. Clustering analysis identified seven groups and defined dozens of corresponding transcription factors, providing a global view of cellular differentiation from primordial germ cells toward meiocytes. Furthermore, we explored the dynamics of gene expression within the developmental trajectory with special focus on the critical state of meiosis. We found that meiosis initiation occurs as early as E12.5 and the cluster of oogonia_4 is the critical state between mitosis and meiosis. Our data provide key insights into the transcriptome features of peri‐meiotic female germ cells, which offers new information not only on meiosis initiation and progression but also on screening pathogenic mutations in meiosis‐associated diseases.

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“…This assumption is supported by a recent study using embryonal day 8.5 mouse embryos. When treated with RA, SALL4 was identified as one of the most severely down-regulated genes in the presomitic mesoderm (28). In our ChIP assays, ATRA treatment also led to decreased SALL4 binding to target genes and dissociation of SALL4 and epigenetic corepressors from RAR␣ (Fig.…”

Section: Discussionmentioning

confidence: 60%

Knockdown of SALL4 Protein Enhances All-trans Retinoic Acid-induced Cellular Differentiation in Acute Myeloid Leukemia Cells

Liu

Leung

et al. 2015

Journal of Biological Chemistry

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Background: SALL4 plays important roles in hematopoiesis and leukemogenesis, including at the stem cell level. Results: SALL4 blocks ATRA-mediated differentiation through directly suppressing RA receptor ␣ signaling. Conclusion: SALL4 plays an unfavorable role in ATRA-based regimes. Significance: SALL4 contributes to AML pathogenesis by inhibiting differentiation stimuli, reinforcing its role as a therapeutic target in leukemia.

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Identification of novel retinoic acid target genes

Cited by 23 publications

References 83 publications

Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR

Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR

Single‐cell RNA sequencing reveals the landscape of early female germ cell development

Knockdown of SALL4 Protein Enhances All-trans Retinoic Acid-induced Cellular Differentiation in Acute Myeloid Leukemia Cells

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