Promoter profiling and coexpression data analysis identifies 24 novel genes that are coregulated with AMPA receptor genes, GRIAs
Authors: Chong, Allen; Zhang, Zhuo; Choi, Kwok Pui; Choudhary, Vidhu; Djamgoz, Mustafa B. A.; Zhang, Guanglan; Bajic, Vladimir B.
We identified a set of transcriptional elements that are conserved and overrepresented within the promoters of human, mouse, and rat GRIAs by comparing these promoters against a collection of 10,741 gene promoters. Cells regulate functional groups of genes by coordinating the transcriptional and/or posttranscriptional mRNA levels of interacting genes. As such, it is expected that functional groups of genes share the same transcriptional features within their promoters. We found 47 genes whose promoters contain the same combination of transcriptional elements that are overrepresented within the promoters of the GRIA gene family. Coexpressed genes may be transcriptionally coregulated, which in turn suggests that these genes may play complementary roles within a particular functional context. Using microarray expression data, we found 24 (of the 47) genes that share not only a similar promoter profile with GRIAs but also a well-correlated gene expression profile and, thus, we believe these to be coregulated with GRIAs. (c) 2006 Elsevier Inc. All rights reserved.
Sjogren Syndrome-associated lymphomas: an update on pathogenesis and management
BRITISH JOURNAL OF HAEMATOLOGY
Authors: Nocturne, Gaetane; Mariette, Xavier
Primary Sjogren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low-grade B cell non-Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa-associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)-like structures, high TNFSF13B (BAFF) and Flt3-ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto-immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto-antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF-kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen-driven B-cell lymphoma. The control of disease activity by a well-targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.