Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super-enhancers to promote direct cardiac reprogramming

ABSTRACT: The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super-enhancers to promote direct cardiac reprogramming

PROVIDER: PRJNA635457 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11860600.fastq.gz	Fastqsanger.gz
	SRR11860600_1.fastq.gz	Fastqsanger.gz
	SRR11860600_2.fastq.gz	Fastqsanger.gz
	SRR11860601.fastq.gz	Fastqsanger.gz
	SRR11860601_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 26

Similar Datasets

The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super-enhancers to promote direct cardiac reprogramming

Project description:Direct cardiac reprogramming of fibroblasts to cardiomyocytes presents an attractive therapeutic strategy to restore cardiac function following injury. Cardiac reprogramming was initially achieved through the overexpression of the transcription factors Gata4, Mef2c, and Tbx5 (GMT), and later, Hand2 (GHMT) and Akt1 (AGHMT) were found to further enhance this process. Yet, staunch epigenetic barriers severely limit the ability of these cocktails to reprogram adult fibroblasts. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the histone reader PHF7 as the most potent activating factor. Mechanistically, PHF7 localizes to cardiac super-enhancers in fibroblasts, and through cooperation with the SWI/SNF complex, increases chromatin accessibility and transcription factor binding at these sites. Importantly, PHF7 is the first epigenetic factor found to achieve efficient reprogramming in the absence of Gata4. Here, we highlight the underexplored necessity of cardiac epigenetic modifiers, such as PHF7, in harnessing chromatin remodeling complexes to overcome critical barriers to direct cardiac reprogramming.

2021-02-26 | GSE151328 | GEO

The histone reader PHF7 cooperates with the SWI/SNF complex at cardiac super enhancers to promote direct reprogramming.

Project description:Direct cardiac reprogramming of fibroblasts to cardiomyocytes presents an attractive therapeutic strategy to restore cardiac function following injury. Cardiac reprogramming was initially achieved through overexpression of the transcription factors Gata4, Mef2c and Tbx5; later, Hand2 and Akt1 were found to further enhance this process1-5. Yet, staunch epigenetic barriers severely limit the ability of these cocktails to reprogramme adult fibroblasts6,7. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the histone reader PHF7 as the most potent activating factor8. Mechanistically, PHF7 localizes to cardiac super enhancers in fibroblasts, and through cooperation with the SWI/SNF complex, it increases chromatin accessibility and transcription factor binding at these sites. Furthermore, PHF7 recruits cardiac transcription factors to activate a positive transcriptional autoregulatory circuit in reprogramming. Importantly, PHF7 achieves efficient reprogramming in the absence of Gata4. Here, we highlight the underexplored necessity of cardiac epigenetic readers, such as PHF7, in harnessing chromatin remodelling and transcriptional complexes to overcome critical barriers to direct cardiac reprogramming.

| S-EPMC8243412 | biostudies-literature

PHF7 Links H3K4 Methylation to H2A Ubiquitination During Spermiongenesis [RNA-seq]

Project description:Histone ubiquitination has been suggested to serve as a “tag” for nucleosome removal during histone-to-protamine exchange that is essential for chromatin packaging in round spermatids. Here, we screen for putative E3 ligase and identify that the PHF7, containing both RING finger and PHD domains, is critical for H2A ubiquitination and histone removal. Mechanistically, its PHD domain as a histone code reader can specifically bind H3K4me3/me2 and its RING domain as a histone writer can ubiquinate H2A. PHF7 deficiency results in male infertility in mice by generating Phf7 knockout mice using CRISPR-Cas9 technology. Futhermore, we find impaired histone-to-protamine exchange leads to reduced chromatin compaction in Phf7 knockout sperm. Immunostaining and western blot further confirme abnormal retention of core histones and reduced levels of protamine PRM1 and PRM2 in Phf7 knockout sperm. In order to exclude the possibility that Phf7 regulate the expession of protamine, we sorte the round spermatids from WT and Phf7 knockout females for RNA-seq. The transcriptomes in round spermatids are very similar between WT and Phf7 knockout mice. There are few differentially expressed genes in the two groups and the expression of protamine is also unchanged even if PHF7 deficiency. Therefore we find PHF7 has no effects on gene regulation in histone-to-protamine exchange.

2019-07-05 | GSE119701 | GEO

PHF7 Links H3K4 Methylation to H2A Ubiquitination During Spermiongenesis

Project description:Histone ubiquitination has been suggested to serve as a “tag” for nucleosome removal during histone-to-protamine exchange that is essential for chromatin packaging in round spermatids. Here, we screen for putative E3 ligase and identify that the PHF7, containing both RING finger and PHD domains, is critical for H2A ubiquitination and histone removal. Mechanistically, its PHD domain as a histone code reader can specifically bind H3K4me3/me2 and its RING domain as a histone writer can ubiquinate H2A. So we want to use ChIP-seq to see whether all PHF7-binding peaks overlapped with those of H3K4me3. We report the application of ChIP-seq for high-throughput profiling of histone modifications in spermatids. By obtaining over 240M of sequences from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps and PHF7 binding position of late spermatids. We find binding peaks of PHF7, H3K4me3 and ub-H2A were mainly enriched at gene-regulatory elements (-5kb to +5kb from transcriptional start site), including promoter and enhancers, indicative of important roles in gene regulations. More than 96% (n=15419) of all PHF7-binding peaks overlapped with those of H3K4me3, supporting a specific binding of PHF7 to H3k4me3. Moreover, the common binding sites between PHF7 and H3K4me3 were associated with ub-H2A. Taken together, these results demonstrate that PHF7 ubiquitinate H2A through binding with H3K4me3.

2019-07-05 | GSE112912 | GEO

PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

Project description:Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system.

2020-07-28 | GSE136752 | GEO

PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression

Project description:PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression

| PRJNA748399 | ENA

Transcriptome analysis of bam- vs. Phf7-,bam- mutant testes

Project description:High-throughput sequencing was used to determine the RNA profiles of the designated genotypes to identify genes with significant expression changes upon deletion of the male germline gene Phf7 in the fruit fly testis.

2017-09-01 | GSE98966 | GEO

PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression[CUT&RUN]

Project description:PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression[CUT&RUN]

| PRJNA1121263 | ENA

PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [RNA-seq]

Project description:PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [RNA-seq]

| PRJNA748393 | ENA

PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [ATAC-seq]

Project description:PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [ATAC-seq]

| PRJNA748402 | ENA