Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment

Yang, Xuexian O.; Angkasekwinai, Pornpimon; Zhu, Jinfang; Peng, Juan; Liu, Zhiduo; Nurieva, Roza; Liu, Xikui; Chung, Yeonseok; Chang, Seon Hee; Sun, Bing; Dong, Chen

doi:10.1038/ni.1821

Cited by 83 publications

(85 citation statements)

References 41 publications

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“…In exploring the transcriptional networks that lead to proper T cell differentiation, potential trans upstream regulators of Gata3 have been proposed (1,12,31,50,51). However, while Gata3 proximal promoter sequences are capable of activating its transcription in transfection experiments (14), we report here that neither of the Gata3 promoters (4) is capable of conferring such activity in vivo.…”

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confidence: 69%

An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene

Hosoya-Ohmura

Lin

Herrmann

et al. 2011

Molecular and Cellular Biology

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Transcription factor GATA-3 is vital for multiple stages of T cell and natural killer (NK) cell development, and yet the factors that directly regulate Gata3 transcription during hematopoiesis are only marginally defined. Here, we show that neither of the Gata3 promoters, previously implicated in its tissue-specific regulation, is alone capable of directing Gata3 transcription in T lymphocytes. In contrast, by surveying large swaths of DNA surrounding the Gata3 locus, we located a cis element that can recapitulate aspects of the Gata3-dependent T cell regulatory program in vivo. This element, located 280 kbp 3 to the structural gene, directs both T cell-and NK cell-specific transcription in vivo but harbors no other tissue activity. This novel, distant element regulates multiple major developmental stages that require GATA-3 activity.

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mentioning

confidence: 69%

An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene

Hosoya-Ohmura

Lin

Herrmann

et al. 2011

Molecular and Cellular Biology

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“…JunB is critical for Th2 differentiation (35)(36)(37). JunB expression is positively regulated by the ERK pathway (38).…”

Section: Discussionmentioning

confidence: 99%

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

Górska

Goplen²,

Qiang³

et al. 2010

The Journal of Immunology

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The Th2 bias is a hallmark of allergic diseases. In this study, we show that the Th1 versus Th2 balance and the development of allergic asthma are strongly affected by the signaling protein uncoordinated 119 (Unc119). The expression of this adaptor protein is significantly increased in Th2 cells. Unc119 activates the Src family and inhibits the Abl family of tyrosine kinases. The activated Src family kinase Lck stimulates the activity of Itk and the expression of the transcription factor JunB. As a result, Unc119 promotes IL-4 production. Through inhibition of Abl kinases, Unc119 dampens IFN-γ production. Using adoptive transfer of Unc119-knockdown CD4 T cells, we show a critical role for Unc119 in the development of eosinophilic inflammation of airways, mucus production, and bronchial hyperreactivity in a mouse model. Intriguingly, the expression of the Unc119 protein is enhanced in CD4 T cells from patients with asthma. We speculate that the heightened expression of Unc119 promotes Th2, inhibits Th1 differentiation, and contributes to the pathogenesis of asthma in humans.

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“…Real-time PCR was performed with TaqMan probe or SYBR Green dye on an ABI Prism 7000 system (Applied Biosystems). Primers used were as follows: HPRT, 36 GATA-3, 37 and GATA-2: forward 5Ј-GCAGAGAAGCAAGGCTCGC-3Ј and reverse 5Ј-CAGTTGACACACTCCCGGC-3Ј; MEF, 38 FOXO3A, 39 c-Myc and NMyc, 13 EGR1, 11 JUNB, 12 and GFI1 (Mm00515855_m1; Applied Biosystems) and GFI1B (Mm00492319_m1; Applied Biosystems). All results of qRT-PCR were quantified relative to the mRNA expression of the endogenous reference gene Hprt for SYBRGreen assay or ribosomal RNA for TaqMan assay (Applied Biosystems).…”

Section: Qrt-pcrmentioning

confidence: 99%

GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

Ku¹,

Hosoya²,

Maillard

et al. 2012

Blood

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IntroductionMultiple hematopoietic cell lineages are generated from hematopoietic stem cells (HSCs) that are found in a very small fraction of the Lin Ϫ Sca1 ϩ c-Kit hi (LSK) population of BM cells. Long-term repopulating HSCs (LT-HSCs) are even more rare, and can be purified almost to homogeneity in the LSK CD150 ϩ CD48 Ϫ CD34 Ϫ Flt3 Ϫ immunophenotypic population of murine adult BM cells. [1][2][3] Less than 5% of LT-HSCs are actively cycling in the S ϩ G 2 /M phases to produce more HSCs for maintaining life-long hematopoiesis and for the generation of terminally differentiated hematopoietic cells.Conversely, approximately 75% of LT-HSCs are quiescent (in the G 0 phase), thus maintaining both stemness and proliferative capacity. 4,5 Studies using various mutant model mice support the contention that the maintenance of HSC quiescence is essential for their long-term repopulating function. 6 The balance between quiescence and cell-cycle entry is controlled by signals from the HSC niche through a variety of signaling pathways, cyclin-dependent kinases, and transcription factors. The molecular mechanisms that control HSC cell-cycle entry are not fully understood, although recent studies have identified several nuclear proteins that are involved in restricting or promoting cell-cycle entry; these include: GFI1, 7 MEF/ELF4, 8 FOXO3A, 9 GFI1B, 10 EGR1, 11 JUNB, 12 and perhaps both c-and N-Myc. 13 The GATA transcription factors all bind to a WGATAR DNA sequence motif found in the promoters and enhancers of thousands of target genes to control their transcription. Recent genome-wide ChIP-seq experiments confirmed that WGATAA is the preferred sequence bound by GATA proteins in vivo. [14][15][16][17] The vertebrate GATA family is composed of 6 members, somewhat artificially divided into the hematopoietic (GATA-1, GATA-2, and GATA-3) and endodermal (GATA-4, GATA-5, and GATA-6) subfamilies. GATA-2 and GATA-3 are both expressed in HSCs. [18][19][20][21] Whereas Gata2-null mutant embryonic stem (ES) cells fail to generate HSCs or progenitors in reconstituted chimeric mice, 22 Gata3-null ES cells are able to generate myeloid and B-lymphoid cells, but not T cells. 23 Therefore, GATA-2 is required for the generation of HSCs, but GATA-3 is not. More specifically, GATA-2 is required for HSC proliferation and viability during definitive hematopoiesis, and even haploinsufficiency of GATA-2 results in a reduced number of functional HSCs. 22,24-26 GATA-3 is vital for the development of T cells at multiple stages in T-cell development and for Th2 differentiation in peripheral organs, but is dispensable for the generation of myeloid and B cells. 27 We recently discovered that GATA-3 is required for the generation of early T-lineage progenitor (ETP) cells, the most immature cells in the thymus, which have been shown to have complete developmental potential for T-lineage development, and that GATA-3 plays a critical role immediately around the time of thymic entry of T-cell progenitors. 28 To further explore a possible role for GATA-3 in ...

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Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment

Cited by 83 publications

References 41 publications

An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene

An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene

Uncoordinated 119 Preferentially Induces Th2 Differentiation and Promotes the Development of Asthma

GATA-3 regulates hematopoietic stem cell maintenance and cell-cycle entry

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