Dataset Information

CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein.

ABSTRACT: TLR2 signaling by Mycobacterium tuberculosis 19-kDa lipoprotein (LpqH) inhibits IFN-gamma-induced expression of CIITA by macrophages. Microarray analysis, quantitative RT-PCR, and Western blots showed that LpqH induced C/EBPbeta and C/EBPdelta in kinetic correlation with inhibition of CIITA expression. Of the C/EBPbeta isoforms, liver inhibitory protein (LIP) was notably induced and liver-activating protein was increased by LpqH. Putative C/EBP binding sites were identified in CIITA promoters I and IV (pI and pIV). LpqH induced binding of C/EBPbeta (LIP and liver-activating protein) to biotinylated oligodeoxynucleotide containing the pI or pIV binding sites, and chromatin immunoprecipitation showed that LpqH induced binding of C/EBPbeta and C/EBPdelta to endogenous CIITA pI and pIV. Constitutive expression of C/EBPbeta LIP inhibited IFN-gamma-induced CIITA expression in transfected cells. In summary, LpqH induced expression of C/EBPbeta and C/EBPdelta, and their binding to CIITA pI and pIV, in correlation with inhibition of IFN-gamma-induced expression of CIITA in macrophages, suggesting a role for C/EBP as a novel regulator of CIITA expression.

SUBMITTER: Pennini ME

PROVIDER: S-EPMC2631233 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein.

Pennini Meghan E ME Liu Yi Y Yang Jianqi J Croniger Colleen M CM Boom W Henry WH Harding Clifford V CV

Journal of immunology (Baltimore, Md. : 1950) 20071101 10

TLR2 signaling by Mycobacterium tuberculosis 19-kDa lipoprotein (LpqH) inhibits IFN-gamma-induced expression of CIITA by macrophages. Microarray analysis, quantitative RT-PCR, and Western blots showed that LpqH induced C/EBPbeta and C/EBPdelta in kinetic correlation with inhibition of CIITA expression. Of the C/EBPbeta isoforms, liver inhibitory protein (LIP) was notably induced and liver-activating protein was increased by LpqH. Putative C/EBP binding sites were identified in CIITA promoters I ...[more]

PMID: 17982082

Similar Datasets

Project description:α-Synuclein is the main component of Lewy bodies, the intracellular protein aggregates representing the histological hallmark of Parkinson's disease. Elevated α-synuclein levels and mutations in SNCA gene are associated with increased risk for Parkinson's disease. Despite this, little is known about the molecular mechanisms regulating SNCA transcription. CCAAT/enhancer binding protein (C/EBP) β and δ are b-zip transcription factors that play distinct roles in neurons and glial cells. C/EBPβ overexpression increases SNCA expression in neuroblastoma cells and putative C/EBPβ and δ binding sites are present in the SNCA genomic region suggesting that these proteins could regulate SNCA transcription. Based on these premises, the goal of this study was to determine if C/EBPβ and δ regulate the expression of SNCA. We first observed that α-synuclein CNS expression was not affected by C/EBPβ deficiency but it was markedly increased in C/EBPδ-deficient mice. This prompted us to characterize further the role of C/EBPδ in SNCA transcription. C/EBPδ absence led to the in vivo increase of α-synuclein in all brain regions analyzed, both at mRNA and protein level, and in primary neuronal cultures. In agreement with this, CEBPD overexpression in neuroblastoma cells and in primary neuronal cultures markedly reduced SNCA expression. ChIP experiments demonstrated C/EBPδ binding to the SNCA genomic region of mice and humans and luciferase experiments showed decreased expression of a reporter gene attributable to C/EBPδ binding to the SNCA promoter. Finally, decreased CEBPD expression was observed in the substantia nigra and in iPSC-derived dopaminergic neurons from Parkinson patients resulting in a significant negative correlation between SNCA and CEBPD levels. This study points to C/EBPδ as an important repressor of SNCA transcription and suggests that reduced C/EBPδ neuronal levels could be a pathogenic factor in Parkinson's disease and other synucleinopathies and C/EBPδ activity a potential pharmacological target for these neurological disorders.

Dataset Information

CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein.

Publications

CCAAT/enhancer-binding protein beta and delta binding to CIITA promoters is associated with the inhibition of CIITA expression in response to Mycobacterium tuberculosis 19-kDa lipoprotein.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets