Both copy number and sequence variations affect expression of human DEFB4.
Genes Immun
; 11(6): 458-66, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-20445567
ABSTRACT
Copy number variations (CNVs) were found to contribute massively to the variability of genomes. One of the best studied CNV region is the beta-defensin cluster (DEFB) on 8p23.1. Individual DEFFB copy numbers (CNs) between 2 and 12 were found, whereas low CNs predispose for Crohn's disease. A further level of complexity is represented by sequence variations between copies (multisite variations, MSVs). To address the relation of DEFB CN and MSV to the expression of beta-defensin genes, we analyzed DEFB4 expression in B-lymphoblastoid cell lines (LCLs) and primary keratinocytes (normal human epidermal keratinocyte, NHEK) before and after stimulation with lipopolysaccharide, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Moreover, we quantified one DEFB4 MSV in DNA and mRNA as a marker for variant-specific expression (VSE) and resequenced a region of approximately 2 kb upstream of DEFB4 in LCLs. We found a strong correlation of DEFB CN and DEFB4 expression in 16 LCLs, although several LCLs with very different CNs exhibit similar expression levels. Quantification of the MSV revealed VSE with consistently lower expression of one variant. Costimulation of NHEKs with TNF-alpha/IFN-gamma leads to a synergistic increase in total DEFB4 expression and suppresses VSE. Analysis of the DEFB4 promoter region showed remarkably high density of sequence variabilities (approximately 1 MSV/41 bp).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Beta-Defensinas
/
Variaciones en el Número de Copia de ADN
Límite:
Humans
Idioma:
En
Revista:
Genes Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Año:
2010
Tipo del documento:
Article
País de afiliación:
Alemania