Interplay between chromatin remodeling and epigenetic changes during lineage-specific commitment to granzyme B expression.
The role of chromatin remodeling and histone posttranslational modifications and how they are integrated to control gene expression during the acquisition of cell-specific functions is poorly understood. We show here that following in vitro activation of CD4(+) and CD8(+) T lymphocytes, both cell types show rapid histone H3 loss at the granzyme B (gzmB) proximal promoter region. However, despite the gzmB proximal promoter being remodeled in both T cell subsets, only CD8(+) T cells express high levels of gzmB and display a distinct pattern of key epigenetic marks, notably differential H3 acetylation and methylation. These data suggest that for high levels of transcription to occur a distinct set of histone modifications needs to be established in addition to histone loss at the proximal promoter of gzmB.
Juelich
Torsten
T
Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Sutcliffe
Elissa L
EL
Sutcliffe
Elissa
E
Denton
Alice
A
He
Yiqing
Y
Doherty
Peter C
PC
Parish
Christopher R
CR
Parish
Christopher
C
Turner
Stephen J
SJ
Turner
Steven J
SJ
Tremethick
David J
DJ
Tremethick
David
D
Rao
Sudha
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D042002:Chromatin Assembly and Disassembly; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic
D006657:Histones; D012319:RNA Polymerase II; D053804:Granzymes