The Promoter of the Immunoglobulin J Chain Gene Receives Its Authentic Enhancer Activity through the Abutting MEF2 and PU.1 Sites in a DNA-Looping Interaction

Lim, Jung Hyun; Kim, Hong Gi; Park, Sung-Kyun; Kang, Chang-Joong

doi:10.1016/j.jmb.2009.05.040

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…Consistent with these previous studies, we observed significant differential methylation at several immune-related genes with PU.1 binding sites in our meta-analysis, including MS4A6A, MS4A4A, and TREM2 genes as well as the SPI1 gene that encodes PU.1. Interestingly, the most significant DMR identified in this meta-analysis is located on the MAMSTR gene, which encodes a cofactor that interacts with MEF2 75 , a transcription factor that cooperates with PU.1 76,77 .…”

Section: Discussionmentioning

confidence: 94%

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

et al. 2020

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DNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.

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Section: Discussionmentioning

confidence: 94%

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

et al. 2020

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“…It has been shown that IgJ , Igκ , and VDJ rearranged IgH co-localize to the same transcription factories 47 . Furthermore, the expression of IgJ and Igκ is PU.1 regulated and Igκ is silenced in mouse early B cells with Tet2/Tet3 loss 31,48,49 . Altogether, these data suggest that TET2 has a role in regulating immunoglobulin genes in human B cells, possibly through cooperation of TET2 and lineage-specific TFs, and/or through high CXCR4 expression 50 .…”

Section: Discussionmentioning

confidence: 99%

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

et al. 2019

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Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.

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“…Because Ig gene enhancers use several common transcription factors that include E2A, IRF4, and PU.1 (Lim et al 2009;Lin et al 2012;Ochiai et al 2013), we propose that continual dynamic Ig gene sorting to different transcription factories during transcription cycles may result in eventual high Ig gene colocalization owing to the beneficial cooperative sharing of those factors. This mechanism for driving the colocalization of multiple genes into single factories has been supported by mathematical modeling when essential shared transcription factors are limiting (Kang et al 2011).…”

Section: Nuclear Order Of Ig Genes and Transcripts Genes And Developmenmentioning

confidence: 99%

Pronounced cohabitation of active immunoglobulin genes from three different chromosomes in transcription factories during maximal antibody synthesis

et al. 2014

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To understand the relationships between nuclear organization and gene expression in a model system, we employed three-dimensional imaging and chromatin immunoprecipitation (ChIP)-chromosome conformation capture (3C) techniques to investigate the topographies of the immunoglobulin (Ig) genes and transcripts during B-cell development. Remarkably, in plasma cells, when antibody synthesis peaks, active Ig genes residing on three different chromosomes exhibit pronounced colocalizations in transcription factories, often near the nuclear periphery, and display trans-chromosomal enhancer interactions, and their transcripts frequently share interchromatin trafficking channels. Conceptually, these features of nuclear organization maximize coordinated transcriptional and transcript trafficking control for potentiating the optimal cytoplasmic assembly of the resulting translation products into protein multimers.

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The Promoter of the Immunoglobulin J Chain Gene Receives Its Authentic Enhancer Activity through the Abutting MEF2 and PU.1 Sites in a DNA-Looping Interaction

Cited by 9 publications

References 37 publications

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans

Pronounced cohabitation of active immunoglobulin genes from three different chromosomes in transcription factories during maximal antibody synthesis

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