Identification of new Rel/NFκB regulatory networks by focused genome location analysis

NFκB is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NFκB to the promotion and progression of various cancers. Despite extensive interest and characterization, many NFκB controlled genes still remain...

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Guardado en:
Detalles Bibliográficos
Publicado: 2009
Materias:
ATM
ChIP/chip
Ets
NFκB
T-cells
ATM protein
DNA
E1A associated p300 protein
Ets transcription factor
immunoglobulin enhancer binding protein
interstitial collagenase
mitogenic agent
protein p50
RNA
selectin
transcription factor
transcription factor Rel
transforming growth factor beta
unclassified drug
animal cell
article
cell cycle regulation
cell interaction
chromatin immunoprecipitation
comparative study
controlled study
DNA repair
embryo
extracellular matrix
gene
gene expression
gene identification
gene location
genetic analysis
genome
genomic instability
human
human cell
introspection
microarray analysis
mouse
nonhuman
prediction
promoter region
protein analysis
protein deficiency
protein expression
protein function
protein interaction
RNA interference
SFN gene
T lymphocyte
technology
tumor growth
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15384101_v8_n13_p2093_DeSiervi
http://hdl.handle.net/20.500.12110/paper_15384101_v8_n13_p2093_DeSiervi
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:NFκB is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NFκB to the promotion and progression of various cancers. Despite extensive interest and characterization, many NFκB controlled genes still remain to be identified. We used chromatin immunoprecipitation combined with microarray technology (ChIP/chip) to investigate the dynamic interaction of NFκB with the promoter regions of 100 genes known to be expressed in mitogen-induced T-cells. Six previously unrecognized NFκB controlled genes (ATM, EP300, TGFβ, Selectin, MMP-1 and SFN) were identified. Each gene is induced in mitogen-stimulated T-cells, repressed by pharmacological NFκB blockade, reduced in cells deficient in the p50 NFκB subunit and dramatically repressed by RNAi specifically designed against cRel. A coregulatory role for Ets transcription factors in the expression of the NFκB controlled genes was predicted by comparative promoter analysis and confirmed by ChIP and by functional disruption of Ets. NFκB deficiency produces a deficit in ATM function and DNA repair indicating an active role for NFκB in maintaining DNA integrity. These results define new potential targets and transcriptional networks governed by NFκB and provide novel functional insights for the role of NFκB in genomic stability, cell cycle control, cell-matrix and cell-cell interactions during tumor progressio. ©2009 Landes Bioscience.

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