PU.1 as a chromatin accessibility factor for immunoglobulin genes

Marecki, Sylvia; McCarthy, Kevin M.; Nikolajczyk, Barbara S.

doi:10.1016/j.molimm.2003.08.007

Cited by 21 publications

(21 citation statements)

References 37 publications

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“…However, we did not observe a convincing increase in H3 acetylation in response to PU.1 and p300 transfection (data not shown). This is consistent with other work showing that PU.1 does not increase nuclease accessibility at the Ig locus in non-B lineage cells (51). Similarly, we found that stable expression of PU.1 in NIH-3T3 cells did not result in appreciable PU.1 binding at the endogenous Ig locus, suggesting that PU.1 does not gain access to the locus in fibroblasts (data not shown).…”

Section: Discussionsupporting

confidence: 93%

Protein Acetylation Regulates Both PU.1 Transactivation and Igκ 3′ Enhancer Activity

Bai

Srinivasan

Perkins

et al. 2005

The Journal of Immunology

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Igκ gene expression and chromatin structure change during B cell development. At the pre-B cell stage, the locus is relatively hypoacetylated on histone H3, whereas it is hyperacetylated at the plasma cell stage. We find in this study that the histone deacetylase inhibitor, trichostatin A (TSA) stimulated 3′ enhancer activity through the PU.1 binding site. TSA also stimulated PU.1 transactivation potential. PU.1 activity was increased by the coactivator acetyltransferase protein, p300, and p300 physically interacted with PU.1 residues 7–30. PU.1 served as a substrate for p300 and was acetylated on lysine residues 170, 171, 206, and 208. Mutation of PU.1 lysines 170 and 171 did not affect PU.1 DNA binding, but did lower the ability of PU.1 to activate transcription in association with p300. Lysine 170 was acetylated in pre-B cells and plasmacytoma cells, but TSA treatment did not stimulate PU.1 acetylation at this residue arguing that a second mechanism can stimulate 3′ enhancer activity. Using chromatin immunoprecipitation assays we found that TSA caused preferential acetylation of histone H3 at the 3′ enhancer. The relevance of these studies for PU.1 function in transcription and hemopoietic development is discussed.

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Section: Discussionsupporting

confidence: 93%

Protein Acetylation Regulates Both PU.1 Transactivation and Igκ 3′ Enhancer Activity

Bai

Srinivasan

Perkins

et al. 2005

The Journal of Immunology

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“…Finally, the −676T (which completely linked with −1187T) allele, but not −676G (which completely linked with −1187C), has a binding site for the transcription factor PU.1, which is a member of the ets transcription factor family that activates gene transcription. Studies have shown that PU.1 is required for normal blood cell development, and abnormalities of the PU.1 gene can lead to leukemia [37][38][39]. Taken together, the results of bioinformatics analysis suggest that the presence of genetic variants in the H2AFX promoter region predicts risk of developing breast cancer and is consistent with the findings in the present study.…”

Section: Discussionsupporting

confidence: 90%

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged ≤55 years

Wei

Bondy

Brewster

et al. 2007

Breast Cancer Res Treat

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The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., −1654A > G [rs643788], −1420G > A [rs8551], and −1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3′ untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged ≤55 years. We found that significantly increased risk of breast cancer was associated with variant genotypes in the H2AFX promoter: adjusted odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.38-2.34 for −1654AG/GG; OR = 1.40, 95% CI = 1.07-1.83 for −1420GA/AA; and OR = 1.65, 95% CI = 1.26-2.16 for −1187TC/CC. Furthermore, the number of variant alleles in the promoter haplotypes was associated with increased risks of breast cancer in a dose-response manner (OR = 6.08, 95% CI = 3.25-11.38; OR = 6.83, 95% CI = 3.83-12.18; and OR = 23.61, 95% CI = 3.95-140.99 for one, two, and three variant alleles, respectively) (P trend < 0.0001). Age at onset of breast cancer significantly decreased as the number of variant alleles increased (P trend = 0.024). However, these effects were not observed in the 3′UTR 1057C > T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of

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“…If so, the poised promoter architecture must be established in a very early multipotent precursor, unless HSCs activate the locus using alternative mechanisms. Furthermore, because PU.1 can act as a chromatin accessibility factor in other contexts (28,49), and ectopic PU.1 expression can induce IL-1␤ from the endogenous locus in nonhematopoietic cells (8), PU.1 is a likely candidate for establishing the poised chromatin structure. HSCs express PU.1 (50,51).…”

Section: Discussionmentioning

confidence: 99%

The Interleukin-1β Gene Is Transcribed from a Poised Promoter Architecture in Monocytes

Liang

Zhang

McDevit

et al. 2006

Journal of Biological Chemistry

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Cytokine transcription is usually regulated by transcription factor binding and chromatin remodeling following an inducing signal. By contrast, these data showed the interleukin (IL)-1␤ promoter assembles into a "poised" structure, as evidenced by nuclease accessibility and loss of core histones immediately surrounding the transcription start site. Strikingly, these properties do not change upon transcriptional activation by lipopolysaccharide. Furthermore, association of two key transcriptional activators, PU.1 and C/EBP␤, is robust pre-and post-stimulation indicating the IL-1␤ promoter is packaged into a nontranscribed but poised promoter architecture in cells capable of rapidly inducing IL-1␤. Monocyte stimulation causes recruitment of a third factor, IRF-4, to the IL-1␤ enhancer. PU.1 phosphorylation at a CK2 kinase consensus element is required for this recruitment. We showed that CK2 phosphorylates PU.1, CK2 inhibitors abrogate IL-1␤ induction, and CK2 inducibly associates with the IL-1␤ enhancer. Taken together, these data indicate a novel two-step mechanism for IL-1␤ transcription: 1) formation of a poised chromatin architecture, and 2) phosphorylation of an enhancer-bound factor that recruits other activators. We propose that this poised structure may generally characterize rapidly activated genes.

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PU.1 as a chromatin accessibility factor for immunoglobulin genes

Cited by 21 publications

References 37 publications

Protein Acetylation Regulates Both PU.1 Transactivation and Igκ 3′ Enhancer Activity

Protein Acetylation Regulates Both PU.1 Transactivation and Igκ 3′ Enhancer Activity

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged ≤55 years

The Interleukin-1β Gene Is Transcribed from a Poised Promoter Architecture in Monocytes

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