GM-CSF inducesSTAT5 binding at epigentic regulatory sites within the Csf2 promoter of non-obese diabetic(NOD) mouse myeloid cells

Granulocyte-macrophage colony stimulating factor(GM-CSF) is a cytokine signal that can advance the myeloid previous cells into granulocytes, monocytes,macrophages and dendritic cells during their differentiation and the inflammation. The expression of this factor is strictly regulated, and its effection is much more dominant than other two factors, macrophage colony stimulating factor(M-CSF) and granulocyte colony stimulating factor(G-CSF) in myeloid cell differentiation. The response of inflammation in mature myeloid cells is to product GM-CSF that maintain the activation of PGS2 and COX2. GM-CSF is also an inducor of IL- 10 producton. It is believed that cytokine-induced epigenetic control of GM-CSF ‘s DNA coding upstream area involved Csf2 promoter that contain some special sites for the histone deacetylase is playing a vital role to ragulate the resposnsiveness and expression of GM-CSF.

GM-CSF is highly expressed in myeloid antigen presenting cells(APC) in both autoimmune type 1 diabetes(T1D) patients and the non-obese diabetic mouse, which can activate two proteins STAT5A and STAT5B. STAT5 proteins can also be regulated by M-CSF during the expression of myeloid cell DNA, so the over-stimulation of GM-CSF to those two proteins could cause APC‘s lack of responsiveness to M-CSF.

The GM-CSF regulatory function to STAS5 proteins is that it maintains the STAT5 proteins with binding sites on the upstream of GM-CSF coding gene Csf2, an non-coding area that reported as a part of epigenetic chromatin modification sites. It has been testified that in NOD mature macrophages and immature bone marrow cells, STAT5 proteins bind at those sites, which is sitmulated by GM-CSF, can have a positive effection to its own gene expression, and also could explain the highly expressed GM-CSF and the lag of activation of STAT5.

Kai Zhang

 

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