RNA-seq analysis from epididymis and testis of ArKI mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE112697 | GEO | 2019/01/09
REPOSITORIES: GEO
Similar Datasets
Project description:To analyze how SUMOylation of AR affects its chromatin binding, we generated a mouse model (ArKI) in which the two conserved SUMO acceptor lysines of androgen receptor (AR) were permanently abolished by converting them to arginines (ArK381R, K500R). ChIP-seq was used to analyse how the lack of AR SUMOylation affects the chromatin binding of AR in epididymis.
2019-01-09 | GSE121151 | GEO
Project description:Our findings demonstrate beneficial effects of enhancing transactivation function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may provide new targets for therapeutic intervention. We mutated conserved lysines in the polyQ AR that are targeted by SUMO, a modification that inhibits AR transactivation function.
2015-12-21 | E-GEOD-60691 | biostudies-arrayexpress
Project description:Signal transduction by Small Ubiquitin-like Modifier (SUMO) regulates a myriad of nuclear processes. Here, we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery resulted in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identified the APC/C complex, a master regulator of metaphase to anaphase transition, as a SUMO target. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation increased APC/C ubiquitylation activity towards a subset of its targets, including the newly identified target KIF18B. Intriguingly, SUMOylation of APC/C was regulated by casein kinase driven phosphorylation of serines at positions 777 and 779. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal a triad of PTMs, cooperating to drive mitosis.
2018-09-19 | PXD006335 | Pride
Project description:Phylogenetically conserved lysines 419 and 845 of zebrafish Zbtb21 protein can be conjugated with SUMO molecules. SUMOylation does not affect the subcellular localization and protein stability of Zbtb21, as well as the interaction with Zbtb14 or Zbtb21. Nevertheless, luciferase reporter assays revealed that Zbtb21 is a dual-function transcription factor which exerts activation or repression effect on different promoters, and SUMOylation can modulate the transcriptional activity of Zbtb21 in regulating downstream target genes. Hence, Zbtb21 is identified as a novel substrate of SUMOylation, which would be important for its function.
2024-04-06 | GSE255803 | GEO
Project description:Phylogenetically conserved lysines 419 and 845 of zebrafish Zbtb21 protein can be conjugated with SUMO molecules. SUMOylation does not affect the subcellular localization and protein stability of Zbtb21, as well as the interaction with Zbtb14 or Zbtb21. Nevertheless, luciferase reporter assays revealed that Zbtb21 is a dual-function transcription factor which exerts activation or repression effect on different promoters, and SUMOylation can modulate the transcriptional activity of Zbtb21 in regulating downstream target genes. Hence, Zbtb21 is identified as a novel substrate of SUMOylation, which would be important for its function.
2024-04-06 | GSE254892 | GEO
Project description:Small ubiquitin-like modifiers (SUMOs) are post-translational modifications (PTMs) that regulate nuclear cellular processes. Here we used an augmented K0–SUMO proteomics strategy to identify 40,765 SUMO acceptor sites and quantify their fractional contribution for 6,747 human proteins. Structural–predictive analyses revealed that lysines residing in disordered regions are preferentially targeted by SUMO, in notable contrast to other widespread lysine modifications. In our data set, we identified 807 SUMOylated peptides that were co-modified by phosphorylation, along with dozens of SUMOylated peptides that were co-modified by ubiquitylation, acetylation and methylation. Notably, 9% of the identified SUMOylome occurred proximal to phosphorylation, and numerous SUMOylation sites were found to be fully dependent on prior phosphorylation events. SUMO-proximal phosphorylation occurred primarily in a proline-directed manner, and inhibition of cyclin-dependent kinases dynamically affected co-modification. Collectively, we present a comprehensive analysis of the SUMOylated proteome, uncovering the structural preferences for SUMO and providing system-wide evidence for a remarkable degree of cross-talk between SUMOylation and other major PTMs. (part 2)
2017-01-24 | PXD005296 | Pride
Project description:Small ubiquitin-like modifiers (SUMOs) are post-translational modifications (PTMs) that regulate nuclear cellular processes. Here we used an augmented K0–SUMO proteomics strategy to identify 40,765 SUMO acceptor sites and quantify their fractional contribution for 6,747 human proteins. Structural–predictive analyses revealed that lysines residing in disordered regions are preferentially targeted by SUMO, in notable contrast to other widespread lysine modifications. In our data set, we identified 807 SUMOylated peptides that were co-modified by phosphorylation, along with dozens of SUMOylated peptides that were co-modified by ubiquitylation, acetylation and methylation. Notably, 9% of the identified SUMOylome occurred proximal to phosphorylation, and numerous SUMOylation sites were found to be fully dependent on prior phosphorylation events. SUMO-proximal phosphorylation occurred primarily in a proline-directed manner, and inhibition of cyclin-dependent kinases dynamically affected co-modification. Collectively, we present a comprehensive analysis of the SUMOylated proteome, uncovering the structural preferences for SUMO and providing system-wide evidence for a remarkable degree of cross-talk between SUMOylation and other major PTMs. (part 1)
2017-01-24 | PXD004927 | Pride
Project description:Expansion of a polyglutamine (polyQ) tract in the gene for the androgen receptor (AR) results in partial loss of transactivation function and causes spinobulbar muscular atrophy (SBMA). Modification of AR by small ubiquitin-like modifier (SUMO) reduces AR function in a promoter context-dependent manner. We used microarrays to confirm and demonstrate loss of AR function from polyQ expansion and to test the degree to which AR function is altered by preventing polyQ AR SUMOylation. PC12 cells expressing AR10Q, AR112Q, or nonSUMOylatable AR112Q (KRKR) in the presence or absence of synthetic androgen R1881 were assessed for alterations in AR function by comparing gene expression changes with each AR variant in response to ligand.
2014-08-23 | E-GEOD-50383 | biostudies-arrayexpress
Project description:Expansion of a polyglutamine (polyQ) tract in the gene for the androgen receptor (AR) results in partial loss of transactivation function and causes spinobulbar muscular atrophy (SBMA). Modification of AR by small ubiquitin-like modifier (SUMO) reduces AR function in a promoter context-dependent manner. We used microarrays to confirm and demonstrate loss of AR function from polyQ expansion and to test the degree to which AR function is altered by preventing polyQ AR SUMOylation.
2014-08-23 | GSE50383 | GEO
Project description:The chromatin organizers Satb1 and Satb2 regulate developmental genes in a tissue- and locus-specific manner. In mouse Embryonic Stem Cells (mESCs), the Satb proteins are involved in the balance between pluripotency and differentiation by direct control of key developmental factors such as Nanog and a number of Hox genes. Despite their structural similarities, the Satb proteins regulate mESC pluripotency in opposing ways: Satb1 promotes differentiation by repressing Nanog and activating the neural genes Bcl2 and Nestin, while Satb2 supports the pluripotent state by activating Nanog and repressing Satb1. To further address the mechanisms by which the Satb proteins regulate gene expression, we examined the conjugation of Satb2 with the small ubiquitin-like modifier (SUMO) in pluripotent and differentiated mESCs. We describe for the first time the endogenous SUMOylation of Satb2 in mESCs as a response to developmental cues. We found that Satb2 is progressively SUMO2-modified during differentiation of ESCs towards ectodermal precursors. Moreover, we identified Zfp451 as a SUMO E3 ligase able to interact with and modify Satb2 with SUMO2 in vitro and in vivo. Ablation of Zfp451 or mutation of the SUMO-acceptor lysines in the Satb2 protein disrupt the ability of mESCs to efficiently shut-down pluripotency genes and activate the differentiation program. Importantly, forced expression of SUMO2-Satb2 N-terminal fusions rescues the differentiation defect of SUMO-Satb2 deficient mESCs. Mechanistically, SUMOylation reduces binding of Satb2 to a subset of loci associated to pluripotency genes and changes the composition of Satb2-containing complexes in chromatin. Taken together, our data suggests that SUMO modification of the chromatin organizer Satb2 by the E3 ligase Zfp451 is required for the efficient downregulation of pluripotency genes and initiation of the differentiation program in mouse embryonic stem cells.
2021-07-08 | GSE119990 | GEO