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LARP7 suppresses endothelial-to-mesenchymal transition by coupling with TRIM28

ABSTRACT: LARP7 suppresses endothelial-to-mesenchymal transition by coupling with TRIM28

PROVIDER: PRJNA694430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13579685.fastq.gz	Fastqsanger.gz
	SRR13579685_1.fastq.gz	Fastqsanger.gz
	SRR13579685_2.fastq.gz	Fastqsanger.gz
	SRR13579686.fastq.gz	Fastqsanger.gz
	SRR13579686_1.fastq.gz	Fastqsanger.gz

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LARP7 suppresses endothelial-to-mesenchymal transition by coupling with TRIM28

Project description:LARP7 plays a pivotal role in regulating endothelial-to-mesenchymal transition(EndMT) and EndMT-associated heart valve formation. LARP7 directly interactes with TRIM28 and cooperatively represses SLUG transcription, which thereby suppresses EndMT of endothelial cells. More importantly, inducible knockout of LARP7 or TRIM28 in the endocardium promotes EndMT in vivo and leads to the valvular hyperplasia.

2023-09-22 | GSE165400 | GEO

SETDB1-TRIM28 complex suppresses antitumor immunity

Project description:SETDB1-TRIM28 complex suppresses antitumor immunity

| PRJNA755287 | ENA

SETDB1-TRIM28 complex suppresses antitumor immunity [RNA-seq]

Project description:SETDB1-TRIM28 complex suppresses antitumor immunity [RNA-seq]

| PRJNA754434 | ENA

SETDB1-TRIM28 complex suppresses antitumor immunity [CRISPR/Cas9 screen]

Project description:SETDB1-TRIM28 complex suppresses antitumor immunity [CRISPR/Cas9 screen]

| PRJNA755293 | ENA

SETDB1-TRIM28 complex suppresses antitumor immunity [RNA-seq]

Project description:Epigenetic mechanism contributes to immune landscapes in cancer. Here we identify the SETDB1-TRIM28 complex as a critical suppressor of antitumor immunity. An epigenetic CRISPR-Cas9 screen of 1,218 chromatin regulators identified TRIM28 as a novel suppressor of PD-L1 expression. We revealed that expression of the SETDB1-TRIM28 complex negatively correlates with infiltration of effector CD8+ T cells. Inhibition of SETDB1-TRIM28 simultaneously upregulates PD-L1 and activates the cGAS-STING innate immune response to increase infiltration of CD8+ T cells. Mechanistically, SETDB1-TRIM28 inhibition leads to micronuclei formation in cytoplasm, a known activator of the cGAS-STING pathway. Thus, SETDB1-TRIM28 inhibition bridges the innate and adaptive immunity. Indeed, SETDB1 knockout enhances the antitumor effects of immune checkpoint blockade anti-PD-L1 in an ovarian cancer mouse model in a cGAS dependent manner. Our findings establish SETDB1-TRIM28 complex as a regulator of antitumor immunity and its loss activates cGAS-STING innate immunity to boost antitumor effects of immune checkpoint blockades.

2021-10-20 | GSE182089 | GEO

SETDB1-TRIM28 complex suppresses antitumor immunity [CRISPR/Cas9 screen]

2021-10-20 | GSE182197 | GEO

Role of LARP7 in meiotic sex chromosome silencing

Project description:Meiotic sex chromosome inactivation (MSCI) is an essential event in meiotic progression in mammalian spermatogenesis. We found that La Ribonucleoprotein 7 (LARP7) is involved in MSCI. LARP7 plays a role in fetal germ cells to promote their proliferation, but is once abolished in postnatal gonocytes and re-expresses in spermatocytes at the onset of meiosis. In spermatocytes, LARP7 localizes to the XY body, a compartmentalized chromatin domain on sex chromosomes. This study aimed to elucidate a possible function of LARP7 in the XY body by using germline-specific Larp7-deficient mice.

2024-10-01 | GSE261526 | GEO

Identification of small RNAs interacting with LARP7

Project description:The La-related protein LARP7 has been mainly described as a component of the 7SK small nuclear ribonucleoprotein (snRNP) complex, which negatively regulates RNA polymerase II by sequestering the positive transcription elongation factor b (P-TEFb). In our studies, we discovered a novel, 7SK snRNP-independent function of LARP7. We show that LARP7 interacts with the U6 spliceosomal RNA as well as with the small nucleolar RNAs (snoRNAs) directing the 2'-O-methylations of U6. Importantly, in the absence of LARP7, significantly less 2'-O-methylations are deposited on U6 affecting splicing fidelity. Mutations in the LARP7 gene have been associated with the Alazami syndrome, a form of primordial dwarfism characterized by intellectual disability. We describe a novel loss-of-function mutation of LARP7 occurring in Alazami patients and detect reduced 2'-O-methylations of U6 in patient-derived samples. Thus, aberrant posttranscriptional RNA modifications of the spliceosomal U6 snRNA may contribute to the development of this severe disease.

2020-02-03 | GSE126592 | GEO

TRIM28 is an epigenetic barrier to induced pluripotent stem cell reprogramming

Project description:Since the discovery of induced pluripotent stem cells there has been intense interest in understanding the mechanisms that allow a somatic cell to be reprogrammed back to a pluripotent state. Several groups have studied the alterations in gene expression that occur as somatic cells modify their genome to that of an embryonic stem cell. Underpinning many of the gene expression changes are modifications to the epigenetic profile of the associated chromatin. We have used a large-scale shRNA screen to identify epigenetic modifiers that act as barriers to reprogramming. We have uncovered an important role for TRIM28 in cells resisting transition between somatic and pluripotent states. TRIM28 achieves this by maintaining the H3K9me3 repressed state and keeping endogenous retroviruses silenced. We propose that knockdown of TRIM28 during reprogramming results in more plastic H3K9me3 domains, dysregulation of genes nearby H3K9me3 marks, and up regulation of endogenous retroviruses, thus facilitating the transition through reprogramming. Gene expression profiling using high through put sequencing at day 7 of Oct4, Sox2, Klf4 and cMyc (OSKM) expression in mouse embryonic fibroblasts with or without Trim28 / Setdb1 knockdown

2016-06-28 | E-GEOD-80550 | biostudies-arrayexpress

Identify RNAs That are Bound by LARP7

Project description:Anti-LARP7 RNA immunoprecipitation (RIP) coupled with RNA-seq assays showed significant enrichment of U6 snRNA, but not other 4 spliceosomal snRNAs, in LARP7 complexes in adult mouse testis.

2019-11-07 | GSE128831 | GEO

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