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Gene expression profile in Ronin (Thap11) conditional knock out retina through RNA-sequencing

ABSTRACT: Conditional knockout of the transcription factor Ronin (Thap11) in retinal progenitor cells (RPCs) results in a profound failure cell proliferation resulting in a hypoplastic adult retina that also suffers from photoreceptor degeneration. The goal of this study was to determine which genes are deregulated in response to loss of Ronin transcription factor activity in the developing retina. We generated Ronin flox/flox (Control) and Chx10-Cre::GFP+/tg; Ronin flox/flox (CKO) mice, in which Ronin loss occurs specifically within RPCs, and performed RNA-Seq analysis of embryonic day E14.5 (E14.5) retinae. Three independent pools of control and Ronin CKO retinae were collected consisting of a minimum of 10 retinae per pool and total RNA was extracted followed by polyA selection, fractionation (200-500 nucleotide range) and generation of cDNA. The resulting DNA was then used for standard Illumina adaptor ligation and sequencing. This experiment revealed decreased expression of a large group of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle.

ORGANISM(S): Mus musculus

PROVIDER: GSE74822 | GEO | 2016/01/19

SECONDARY ACCESSION(S): PRJNA301605

REPOSITORIES: GEO

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Genome-wide occupancy profiling of Ronin (Thap11) in retinal development

Project description:Conditional knockout of the transcription factor Ronin (Thap11) in retinal progenitor cells (RPCs) results in a profound failure cell proliferation resulting in a hypoplastic adult retina that also suffers from photoreceptor degeneration. The goal of this study was to determine the genes that are transcriptionally regulated by Ronin during retinogenesis. P0 wild type retinae (CD-1 background) were pooled (>10 each) in ice-cold 1X PBS and immediately processed for chromatin extraction, fragmentation and immunoprecipitation using custom antibodies against Ronin G4275 (Dejosez et al., 2010), G4275 preimmune serum or normal rabbit IgG (Santa Cruz, sc-2027). The immunoprecipitated DNA fragments were then sequenced using the Ion Torrent PGM system.

2016-01-19 | GSE74823 | GEO

RNA-seq of mouse embryonic stem cells with Ronin/Thap11 knockout

Project description:RNA-seq of Ronin/Thap11 knockout and heterozygous control mouse ES cells to assess the role of Ronin

2022-01-31 | E-MTAB-10024 | biostudies-arrayexpress

Analysis of Ronin knockout related gene expression changes in mouse embryonic stem cells.

Project description:Ronin knockout is embryonic lethal and Ronin knockout ES cells are not viable. Here we used CreER2; Roninflox/flox mouse ES cells to induce Ronin knockout by tamoxfien treatment in comparison to control Roninflox/flox cells to study Ronin knockout related transcriptional changes.

2018-09-16 | GSE120008 | GEO

RNA-seq of mouse embryonic stem cells with Ronin/Thap11 knockout

Project description:RNA-seq of mouse embryonic stem cells with Ronin/Thap11 knockout

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Ronin governs early heart development by controlling core gene programs

Project description:Ronin (THAP11), an idiosyncratic DNA-binding protein that evolved from a primordial DNA transposon by molecular domestication, recognizes a hyperconserved promoter sequence through which it controls a variety of developmentally and metabolically essential genes in pluripotent stem cells. However, it remains unclear whether Ronin or related THAP proteins perform similar functions elsewhere in development. Here, we present evidence indicating that Ronin performs a novel function within the nascent heart as it arises from the mesoderm and forms a four-chambered organ. We show that Ronin is vital for cardiogenesis during midgestation through its control of a core set of critical genes. The activity of Ronin coincided with the recruitment of its cofactor, Hcf-1, and the elevation of H3K4me3 levels at specific target genes, suggesting the involvement of an epigenetic mechanism. On the strength of these findings, we propose that Ronin activity during cardiogenesis may offer a template that could be used to understand how important gene programs are sustained across different cell types within a developing organ, such as the heart.

2017-09-19 | GSE103959 | GEO

Expression profiling of the Otx2 CKO retina

Project description:In the vertebrate retina, the Otx2 transcription factor plays a crucial role in the cell fate determination of both rod and cone photoreceptors. Otx2 conditional knockout (CKO) mice exhibited a total absence of rods and cones in the retina due to their cell fate conversion to amacrine-like cells. In order to investigate the entire transcriptome regulated by Otx2 in the developing retina, we performed microarray analysis on the Otx2 CKO retina. In order to clarify the molecular role of Otx2 in transcriptional regulation during development, we investigated the expression profile of the Otx2 CKO retina compared with that of the control retina with the genotype Otx2flox/flox;Crx-cre- using microarrays at two time points, P1 and P12.

2011-05-18 | E-GEOD-21900 | biostudies-arrayexpress

Ronin transcriptional target genes in the developing mouse retina

Project description:Ronin transcriptional target genes in the developing mouse retina

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Regulatory architecture of housekeeping genes is driven by promoter assemblies [Ronin]

Project description:Ronin ChIA-PET in R1 mouse ES cells.

2023-04-15 | GSE136144 | GEO

Mus musculus

Project description:Gene expression profile in Ronin (Thap11) conditional knock out retina through RNA-sequencing

| PRJNA301605 | ENA

RNAseq experiments for "THAP11F80L cobalamin disorder-associated mutation reveals normal and pathogenic THAP11 functions in gene expression and cell proliferation"

Project description:Twelve human THAP proteins share the THAP domain, an evolutionary conserved zinc-finger DNA-binding domain. Studies of different THAP proteins have indicated roles in gene transcription, cell proliferation and development. We have analyzed this protein family, focusing on THAP7 and THAP11. We show that human THAP proteins possess differing homo- and heterodimer formation properties and interaction abilities with the transcriptional co-regulator HCF-1. HEK-293 cells lacking THAP7 were viable but proliferated more slowly. In contrast, HEK-293 cells were very sensitive to THAP11 alteration. Nevertheless, HEK-293 cells bearing a human THAP11 mutation identified in a patient suffering from cobalamin disorder (THAP11F80L) were viable although proliferated more slowly. Cobalamin disorder is an inborn vitamin deficiency characterized by neurodevelopmental abnormalities, most often due to biallelic mutations in the MMACHC gene, whose gene product MMACHC is a key enzyme in the cobalamin metabolic pathway. We show that THAP11F80L selectively affected promoter binding by THAP11, having more deleterious effects on a subset of THAP11 targets, and resulting in altered patterns of gene expression. In particular, THAP11F80L exhibited a strong effect on association with the MMACHC promoter and led to a decrease in MMACHC gene transcription, suggesting that the THAP11F80L mutation is directly responsible for the observed cobalamin disorder.

2019-12-20 | GSE138207 | GEO

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