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C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [DNase-Seq]

ABSTRACT: C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [DNase-Seq]

PROVIDER: PRJNA870425 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21138400.fastq.gz	Fastqsanger.gz
	SRR21138401.fastq.gz	Fastqsanger.gz
	SRR21138402.fastq.gz	Fastqsanger.gz
	SRR21138403.fastq.gz	Fastqsanger.gz
	SRR21138404.fastq.gz	Fastqsanger.gz

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C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [DNase-Seq]

Project description:Disease-causing mutations in genes encoding transcription factors (TF) are frequent in hematopoietic malignancies and might affect TF-interactions with respective DNA-binding motifs. Here, we report the characterization of a recurrent somatic mutation c.295T>C in the IRF4 gene in classic Hodgkin lymphoma (cHL) leading to a C99R exchange. IRF4-C99R is located in the center of the IRF4 alpha3-recognition helix contacting the DNA 5´-GAAA-3´ IRF consensus sequence. IRF4-C99R fundamentally alters IRF4 DNA-binding, combining loss-of-binding at canonical IRF motifs and neomorph gain-of-binding at canonical and non-canonical IRF composite elements (CEs), in particular AP-1-IRF-CEs (AICEs). In line, IRF4-C99R profoundly impairs IRF4-dependent plasma cell induction, and specifically up-regulates degenerate-AICE-dependent distinct cHL disease-characteristic genes. These data document an unprecedented mutation-induced shift of TF binding specificity and its impact for lymphoma pathogenesis and TF modulation.

2023-07-19 | GSE211441 | GEO

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [RNA-Seq]

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C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [ChIP-Seq]

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C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [Illumina BeadChip]

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C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma

Project description:C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma

| PRJNA870420 | ENA

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [ChIP-Seq]

Project description:C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [ChIP-Seq]

| PRJNA870426 | ENA

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [RNA-Seq]

Project description:C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [RNA-Seq]

| PRJNA870427 | ENA

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [Illumina BeadChip]

Project description:C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma [Illumina BeadChip]

| PRJNA872553 | ENA

A new type of pathogenic transcription factor mutation targeting interferon regulatory factor 4 (IRF4) in human lymphoma

Project description:We report the characterization of a recurrent somatic mutation c.295T>C (p.C99R) in the Interferon Regulatory Factor 4 (IRF4) gene in human lymphoma in the α3-recognition helix of the IRF4 DNA-binding domain. IRF4-C99R fundamentally alters IRF4 DNA-binding, combining loss-of-binding at canonical IRF motifs and neomorph gain-of-binding at canonical and non-canonical IRF composite elements (CEs). IRF4-C99R thoroughly modifies IRF4 function, blocking IRF4-dependent plasma cell induction, and specifically up-regulating lymphoma-specific genes in a degenerate Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner.

2023-07-21 | E-MTAB-12522 | biostudies-arrayexpress

C99R mutation in IRF4 drives a novel gain of function binding and gene upregulation in classical Hodgkin lymphoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-07-19 | GSE211445 | GEO