Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural basis of specific DNA binding by the transcription factor ZBTB24

ABSTRACT: Structural basis of specific DNA binding by the transcription factor ZBTB24

PROVIDER: PRJNA495154 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR7984040.fastq.gz	Fastqsanger.gz
	SRR7984050.fastq.gz	Fastqsanger.gz
	SRR7984060.fastq.gz	Fastqsanger.gz
	SRR7984041.fastq.gz	Fastqsanger.gz
	SRR7984051.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 26

Similar Datasets

Structural basis of specific DNA binding by the transcription factor ZBTB24

Project description:ZBTB24, encoding a protein of the ZBTB family of transcriptional regulators, is one of four known genes – the other three being DNMT3B, CDCA7 and HELLS – that are mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a genetic disorder characterized by DNA hypomethylation and antibody deficiency. The molecular mechanisms by which ZBTB24 regulates gene expression and the biological functions of ZBTB24 are poorly understood. Here we identified a 12-bp consensus sequence [CT(G/T)CCAGGACCT] occupied by ZBTB24 in the mouse genome. The sequence is present at multiple loci, including the Cdca7 promoter region, and ZBTB24 binding is mostly associated with gene activation. Crystallography and DNA-binding data revealed that the last four of the eight zinc fingers (ZFs) (i.e. ZF5-8) in ZBTB24 confer specificity of DNA binding. Two ICF missense mutations have been identified in the ZBTB24 ZF domain that alter zinc-binding cysteine residues. We demonstrated that the corresponding C382Y and C407G mutations in mouse ZBTB24 abolish specific DNA binding and fail to induce Cdca7 expression. Our analyses indicate, and suggest a structural basis for, the sequence specific recognition by a transcription factor centrally important for the pathogenesis of ICF syndrome.

2019-06-11 | GSE120969 | GEO

Structural basis of specific DNA binding by the transcription factor ZBTB24.

Project description:ZBTB24, encoding a protein of the ZBTB family of transcriptional regulators, is one of four known genes-the other three being DNMT3B, CDCA7 and HELLS-that are mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a genetic disorder characterized by DNA hypomethylation and antibody deficiency. The molecular mechanisms by which ZBTB24 regulates gene expression and the biological functions of ZBTB24 are poorly understood. Here, we identified a 12-bp consensus sequence [CT(G/T)CCAGGACCT] occupied by ZBTB24 in the mouse genome. The sequence is present at multiple loci, including the Cdca7 promoter region, and ZBTB24 binding is mostly associated with gene activation. Crystallography and DNA-binding data revealed that the last four of the eight zinc fingers (ZFs) (i.e. ZF5-8) in ZBTB24 confer specificity of DNA binding. Two ICF missense mutations have been identified in the ZBTB24 ZF domain, which alter zinc-binding cysteine residues. We demonstrated that the corresponding C382Y and C407G mutations in mouse ZBTB24 abolish specific DNA binding and fail to induce Cdca7 expression. Our analyses indicate and suggest a structural basis for the sequence specific recognition by a transcription factor centrally important for the pathogenesis of ICF syndrome.

| S-EPMC6895263 | biostudies-literature

Loss of ZBTB24, a novel non-homologous end-joining protein, impairs class-switch recombination in ICF syndrome

Project description:The autosomal recessive immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a genetically heterogeneous disorder. Despite recent successes in the identification of the underlying gene defects, it is currently unclear how mutations in any of the four known ICF genes cause a primary immunodeficiency. Here we demonstrate that loss of ZBTB24 in B cells from ICF2 patients impairs non-homologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and subtype balance. Mechanistically, we found that ZBTB24 associates with poly(ADP-ribose) polymerase 1 (PARP1) and stimulates auto-poly(ADP-ribosyl)ation of this enzyme. The zinc finger in ZBTB24 binds PARP1-associated poly(ADP-ribose) chains and mediates the PARP1-dependent recruitment of ZBTB24 to DNA breaks. Moreover, by binding to poly(ADP-ribose) chains ZBTB24 protects these moieties from degradation by poly(ADP-ribose) glycohydrolase (PARG). This enhances the poly(ADP-ribose)-dependent interaction between PARP1 and the LIG4/XRCC4 NHEJ complex and promotes NHEJ by facilitating the assembly of this repair complex at DNA breaks. Thus, we uncover ZBTB24 as a regulator of PARP1-dependent NHEJ and class-switch recombination, providing a molecular basis for the immunodeficiency in ICF syndrome.

2020-08-19 | PXD014741 | Pride

Structural basis for pre-miRNA-31 biogenesis

Project description:Structural basis for pre-miRNA-31 biogenesis

| PRJNA957777 | ENA

Structural Basis for Target-Directed MicroRNA Degradation

Project description:Structural Basis for Target-Directed MicroRNA Degradation

| PRJNA540836 | ENA

Transcriptome-wide RNA structure probing reveals the structural basis of Dicer binding and cleavage

Project description:Transcriptome-wide RNA structure probing reveals the structural basis of Dicer binding and cleavage

| PRJNA612494 | ENA

ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation [Infinium]

Project description:The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in modulating gene expression, is being increasingly appreciated. We investigated the interplay between ZBTB24, a zinc-finger protein belonging to the BTB-POZ family of transcription factors, and the de novo DNA methyltransferase DNMT3B. Both factors, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting they are mechanistically linked in some way, but almost nothing is known about ZBTB24. In this study, we identified genomic targets regulated by ZBTB24, and identified its recognition motif, binding to which leads to activation. Chromatin immunoprecipitation in model cell line systems revealed common genes bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function.

2018-07-31 | GSE111681 | GEO

The structural basis for cohesin/CTCF anchored loops

Project description:The structural basis for cohesin/CTCF anchored loops

| PRJNA522775 | ENA

Structural basis of virulence activation in Francisella tularensis

Project description:Structural basis of virulence activation in Francisella tularensis

| PRJNA634110 | ENA