Tag Archives: Cish3

Background Monocyte-derived macrophages and dendritic cells (DCs) are important in inflammatory

Background Monocyte-derived macrophages and dendritic cells (DCs) are important in inflammatory processes and are often utilized for immunotherapeutic approaches. their maturation, they migrate to the periphery and form approximately 5-10% of human leukocytes. Monocytes circulate in the blood stream for several days and then enter to peripheral tissues where they undergo a phenotypic switch and differentiate further into macrophages or dendritic cells (DCs) [1-4]. In tissues, macrophages have a central role to locally phagocytose and destroy pathogens, to obvious senescent cells and to repair tissues after the inflammatory processes [5]. 1246560-33-7 IC50 Activated macrophages show strong inflammatory responses through the high production of pro-inflammatory cytokines and increased endocytic and antigen presentation activity. Similarly to macrophages, DCs are located in peripheral tissues where they encounter and phagocytose microbes. The acknowledgement 1246560-33-7 IC50 of microbial antigen occurs in the immature state of DCs and prospects to a maturation process, after which they have increased antigen presentation but downregulated antigen acknowledgement capacity. The maturation is usually often accompanied with the migration of DCs to secondary lymphoid organs [6] and several murine DC subsets with variable phenotype, function or tissue locations have been reported [7]. The peripheral blood monocytes exhibit a heterogeneous phenotype with respect to their size and nuclear morphology. They can be relatively easily recognized by high expression of the cell surface marker CD14 and can be divided into at least two major subpopulations 1246560-33-7 IC50 according to their CD16 expression [3]. DCs derived from monocytes are particularly important during inflammatory processes and are efficient in stimulating CD4 and CD8 positive T cell responses [8-11]. Recent studies showed that monocytes can also differentiate into macrophages and DCs under non-inflammatory conditions and that several subsets of antigen presenting cells located in antigen capture areas, such as skin, mucosa, gastrointestinal and respiratory track, are in fact derived from monocytes [12,13]. To generate a large number of human macrophages or DCs, monocytes are typically cultured for several days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) alone or GM-CSF with interleukin 4 (IL-4), respectively [14,15]. Although these culture conditions give rise to only one subset of differentiated cells and do not represent the full heterogeneity of macrophages or DCs in vivo, it still is the most efficient way to obtain human antigen presenting cells. Furthermore, monocyte-derived DCs are by far the most common type of cells used in immunotherapeutic clinical methods [16,17]. Histone modifications within promoter regions have an important Cish3 function in regulation of gene expression [18]. The majority of modifications occur at the N-terminal ends of the core histones in a nucleosome. These modifications are often dynamic as well as reversible and have a functional impact on many aspects of chromatin convenience that may determine the transcriptional status of a given gene. One of the most frequent histone modifications is the trimethylation of histone H3 lysine 4 (H3K4me3), which in gene promoters is usually associated with the transcriptional activation, whereas the trimethylation of histone H3 lysine 27 (H3K27me3) generally results in gene silencing. The presence of these two opposing modifications as bivalent marks on promoters is usually often associated with poised gene transcription. Similar to the H3K4me3 mark, the acetylation of lysines on histone H3 (AcH3) is usually often associated with transcriptional activation [18]. How exactly these 1246560-33-7 IC50 combinations of chromatin modifications translate to gene transcription is currently under extensive investigation in several cell types. Transcriptional control is usually further mediated by chromatin 1246560-33-7 IC50 associated proteins; for example H3K4me3 may serve as a docking site for PHD finger domain name and AcH3 for bromodomains [19]. Here we analyzed the histone H3K4me3, AcH3 and H3K27me3 modifications in human monocytes, monocyte-derived macrophages and DCs. To gain insight into the role of these modifications during the differentiation process, we compared genome-wide gene expression profiles with histone changes in promoter regions over the genome. We show that H3K4me3 and AcH3 marks generally correlate well with gene expression and that H3K27me3 is associated with inactive genes. We also show that H3K4me3 levels are increased around the promoters of several marker genes and gene groups during differentiation. In addition, we provide evidence that this chromatin statuses of gene families within genomic clusters, including chemokine and surface receptor genes, are coordinately modified. Results Genome-wide mRNA expression profiles We first recognized the expression profiles of monocytes, macrophages and DCs using the Illumina Human-6 v2 BeadChip.