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Publication : Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta.

First Author  Kayama H Year  2008
Journal  J Biol Chem Volume  283
Issue  18 Pages  12468-77
PubMed ID  18319258 Mgi Jnum  J:136566
Mgi Id  MGI:3796491 Doi  10.1074/jbc.M709965200
Citation  Kayama H, et al. (2008) Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IkappaBzeta. J Biol Chem 283(18):12468-77
abstractText  Toll-like receptors trigger the induction of primary response genes via MyD88-mediated activation of NF-kappaB and other transcription factors. These factors then act in concert with primary response gene products to induce secondary response genes. Although the MyD88 pathway is important for the expression of both primary and secondary response genes, we show that the recruitment of NF-kappaB, RNA polymerase, and the TATA-binding protein is MyD88-dependent only at secondary response genes. This selective dependence correlates with the fact that MyD88 is required for nucleosome remodeling and histone H3K4 trimethylation at secondary response promoters, whereas rapidly induced primary response promoters are assembled into poised MyD88-independent chromatin structures. At a subset of secondary response promoters, IkappaBzeta was identified as a selective regulator of H3K4 trimethylation and preinitiation complex assembly after nucleosome remodeling. These mechanistic distinctions advance our understanding of the diverse molecular cascades that underlie the differential regulation of pro-inflammatory genes.
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