کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2827776 1162465 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of γ-globin gene expression involves signaling through the p38 MAPK/CREB1 pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Regulation of γ-globin gene expression involves signaling through the p38 MAPK/CREB1 pathway
چکیده انگلیسی

In response to sodium butyrate and trichostatin A treatment in erythroid cells, p38 mitogen activated protein kinase (MAPK) mediates fetal hemoglobin (HbF) induction by activating cAMP response element binding protein 1 (CREB1). To expand on this observation, we completed studies to determine the role of p38 MAPK in steady-state γ-globin regulation. We propose that p38 signaling regulates Gγ-globin transcription during erythroid maturation through its downstream effector CREB1 which binds the Gγ-globin cAMP response element (G-CRE). We demonstrated that a loss of p38 or CREB1 function by siRNA knockdown resulted in target gene silencing. Moreover, gain of p38 or CREB1 function augments γ-globin transcription. These regulatory effects were conserved under physiological conditions tested in primary erythroid cells. When the G-CRE was mutated in a stable chromatin environment Gγ-globin promoter activity was nearly abolished. Furthermore, introduction of mutations in the G-CRE abolished Gγ-globin activation via p38 MAPK/CREB1 signaling. Chromatin immunoprecipitation assays (ChIP) demonstrated that CREB1 and its binding partner CREB binding protein (CBP) co-localize at the G-CRE region. These data support the role of p38 MAPK/CREB1 signaling in Gγ-globin gene transcription under steady-state conditions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 47, Issue 1, 15 June 2011, Pages 12–22
نویسندگان
, ,