Long-range regulation of cytokine gene expression

Rowell, Emily; Merkenschlager, Matthias; Wilson, Christopher

doi:10.1016/j.coi.2008.03.012

Cited by 23 publications

(20 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the precise mechanisms underlying the activation-dependent induction of AMWAP are not fully understood, we postulate that PU.1 plays a critical role in AMWAP expression by direct binding to the proximal promoter. Immune-related genes, including cytokines and chemokines, as well as their receptors are often organized in chromosomal clusters or miniclusters (55)(56)(57). In agreement with this concept, the murine AMWAP gene is located in close proximity to a cluster of the chemokine genes Ccl3, Ccl4, Ccl5, Ccl6, and Ccl9.…”

Section: Discussionmentioning

confidence: 99%

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

Karlstetter

Walczak

Weigelt

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

Karlstetter

Walczak

Weigelt

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…TCR stimulation induces rapid acetylation on histones H3 and H4 in the cytokine gene promoters, irrespective of polarizing conditions. The lineage specific maintenance of acetylation depends on cytokine dependent STAT signaling and lineage specific transcriptional activators Tbet and GATA3 [41].…”

Section: The Emergence Of Regulatory Elementsmentioning

confidence: 99%

How are TH1 and TH2 effector cells made?

Amsen

Spilianakis²,

Flavell

2009

Current Opinion in Immunology

141

128

View full text Add to dashboard Cite

SummaryDifferentiation of T H 1 and T H 2-effector cells proceeds through several phases: First, naïve CD4 + precursor cells are instructed to differentiate as appropriate to optimally fight the infectious threat encountered. This process is governed by the IL12 and IL4 cytokines, as well as by signaling through the Notch receptor. In response to these signals, transcription is initiated of lineage specific genes including the Ifnγ and Il4 genes as well as of genes encoding transcriptional regulators, such as Tbet and Gata3. The respective differentiation programs are reinforced by both positive and negative feedback mechanisms. Furthermore, epigenetic modifications of the lineage specific genes result in the emergence of regulatory elements, which control high level lineage restricted expression by both intra-and interchromosomal associations. Together, these mechanisms ensure stable inheritance of the differentiated fate in the numerous progeny of the original naïve CD4 + T cells.

show abstract

“…The Th2 cytokine locus also engages in chromosomal interactions by either intra-or interchromosomal association (35)(36)(37)(38). The Th2 LCR interacts with the promoters of Th2 cytokine genes and enhancers through long-range intrachromosomal interactions (35).…”

mentioning

confidence: 99%

Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation

Hwang

Kim

Lee

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation. T h2 cytokine genes il4, il13, and il5 are clustered in chromosome 5 in human and chromosome 11 in mouse. The expression of the Th2 cytokine genes are coordinately regulated during Th2 cell differentiation. Several different regulatory elements have been shown to play an important role in Th2 cytokine gene expression, including promoters of Th2 cytokine genes, enhancers [conserved noncoding sequence 1 (CNS1)/hypersensitive site 1-3 (HSS1-3), hypersensitive site V (HSV)/CNS2, and intronic enhancer (IE)/ HSII], a silencer (HSIV), and a locus control region (LCR) (1, 2). The functions of these regulatory elements in Th2 cytokine expression in Th2 cells in vivo have been thoroughly investigated in transgenic mice and knockout mice that have targeted deletion in the regulatory elements (3-10). Among these regulatory elements, Th2 LCR has been shown to coordinately regulate Th2 cytokine genes, to induce chromatin remodeling, and to be required for chromosomal interactions (1, 2). The Th2 LCR is located in the introns of the Rad50 gene and is composed of four DNase I hypersensitive sites, including RHS4, RHS5, RHS6, and RHS7 (11,12). In previous studies, we have shown that the Th2 LCR is essential for Th2 cytokine expression and chromosome remodeling in the Th2 cytokine locus and in the pathogenesis of allergic asthma (7,11,13).The entire Th2 cytokine locus undergoes chromatin remodeling during Th2 cell differentiation (1, 2, 14). DNase I hypersensitive sites, which reflect accessibility of chromatin, are developed at the specific regulatory regions during Th2 cell differentiation (15, 16). Histone 3 lysine 9 (H3K9)-acetylation and histone 3 lysine 4 (H3K4)-methylation increase at specific regulatory regions in the Th2 cytokine locus during Th2 cell differentiation (17)(18)(19)(20). Th2 cytokine locus also undergoes DNA demethylation during Th2 cell differentiation (11,(21)(22)(23)(24)(25)(26). Treatment with drugs that cause chromatin modification such as 5-azacytidine or Trichostatin A induces Th2 cytokine expression upon T-cell recep...

show abstract

Long-range regulation of cytokine gene expression

Cited by 23 publications

References 64 publications

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response

How are TH1 and TH2 effector cells made?

Transcription factor YY1 is essential for regulation of the Th2 cytokine locus and for Th2 cell differentiation

Contact Info

Product

Resources

About