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Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish.

ABSTRACT: BACKGROUND:Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however, the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient and PlxnA2-deficient zebrafish embryos in a microarray analysis to identify genes that were differentially expressed when this signaling pathway was disrupted. RESULTS:We uncovered a set of 58 transcripts, and all but 1 were up-regulated in both sema6A and plxnA2 morphants. We validated gene expression changes in subset of candidates that are suggested to be involved in proliferation, migration or neuronal positioning. We further functionally evaluated one gene, rasl11b, as contributing to disrupted proliferation in sema6A and plxna2 morphants. Our results suggest rasl11b negatively regulates proliferation of RPCs in the developing zebrafish eye. CONCLUSIONS:Microarray analysis has generated a resource of target genes downstream of Sema6A/PlxnA2 signaling, which can be further investigated to elucidate the downstream effects of this well-studied neuronal and vascular guidance signaling pathway. Developmental Dynamics 246:539-549, 2017. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Emerson SE

PROVIDER: S-EPMC6322676 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish.

Emerson Sarah E SE St Clair Riley M RM Waldron Ashley L AL Bruno Sierra R SR Duong Anna A Driscoll Heather E HE Ballif Bryan A BA McFarlane Sarah S Ebert Alicia M AM

Developmental dynamics : an official publication of the American Association of Anatomists 20170518 7

<h4>Background</h4>Semaphorin (Sema)/Plexin (Plxn) signaling is important for many aspects of neuronal development, however, the transcriptional regulation imposed by this signaling pathway is unknown. Previously, we identified an essential role for Sema6A/PlxnA2 signaling in regulating proliferation and cohesion of retinal precursor cells (RPCs) during early eye development. This study used RNA isolated from control, Sema6A-deficient and PlxnA2-deficient zebrafish embryos in a microarray analys ...[more]

PMID: 28440030

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Project description:This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer.We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1.A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1.LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon carcinogenesis.

Dataset Information

Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish.

Publications

Identification of target genes downstream of semaphorin6A/PlexinA2 signaling in zebrafish.

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