Developmental and epigenetic regulation of the human TLR3 gene.
The receptor encoded by the human TLR3 gene recognizes double-strand RNAs (dsRNAs) associated with viral infection. TLR3 expression is strongly activated upon differentiation of monocytes to dendritic cells, and can be further stimulated by the dsRNA analog polyinosine:polycytosine (PI:C). We report evidence for developmental regulation of the TLR3 gene. In dendritic cells derived from cord blood, both differentiation- and PI:C-associated TLR3 transcriptional activation are impaired as compared to cells from adults. Consistent with relative expression patterns, chromatin states and remodeling differ between newborn and adult samples. TLR3 expression in newborn dendritic cells exhibits heterocellularity and allelic imbalance (skewing), features characteristic of cis-acting epigenetic control. These findings reveal a new source for variability in innate immune system function and provide a model for further study of perinatal epigenetic transitions during development.
Porrás
Analia
A
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892, United States.
Kozar
Sarah
S
Russanova
Valya
V
Salpea
Paraskevi
P
Hirai
Tazuko
T
Sammons
Nicholas
N
Mittal
Pooja
P
Kim
Ji Young
JY
Ozato
Keiko
K
Romero
Roberto
R
Howard
Bruce H
BH
D000328:Adult; D000375:Aging / Q000187:drug effects / Q000235:genetics; D000483:Alleles; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002851:Chromatography, High Pressure Liquid; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000378:metabolism
D006657:Histones; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C