Dynamic histone variant exchange accompanies gene induction in T cells.
Changes in chromatin composition are often a prerequisite for gene induction. Nonallelic histone variants have recently emerged as key players in transcriptional control and chromatin modulation. While the changes in chromatin accessibility and histone posttranslational modification (PTM) distribution that accompany gene induction are well documented, the dynamics of histone variant exchange that parallel these events are still poorly defined. In this study, we have examined the changes in histone variant distribution that accompany activation of the inducible CD69 and heparanase genes in T cells. We demonstrate that the chromatin accessibility increases that accompany the induction of both of these genes are not associated with nucleosome loss but instead are paralleled by changes in histone variant distribution. Specifically, induction of these genes was paralleled by depletion of the H2A.Z histone variant and concomitant deposition of H3.3. Furthermore, H3.3 deposition was accompanied by changes in PTM patterns consistent with H3.3 enriching or depleting different PTMs upon incorporation into chromatin. Nevertheless, we present evidence that these H3.3-borne PTMs can be negated by recruited enzymatic activities. From these observations, we propose that H3.3 deposition may both facilitate chromatin accessibility increases by destabilizing nucleosomes and compete with recruited histone modifiers to alter PTM patterns upon gene induction.
Sutcliffe
Elissa L
EL
Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Parish
Ian A
IA
He
Yi Qing
YQ
Juelich
Torsten
T
Tierney
M Louise
ML
Rangasamy
Danny
D
Milburn
Peter J
PJ
Parish
Christopher R
CR
Tremethick
David J
DJ
Rao
Sudha
S
D000918:Antibody Specificity / Q000187:drug effects; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002846:Chromatography, Affinity; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D047468:Immunoprecipitation; D019169:Jurkat Cells; D007700:Kinetics; D037181:Lectins, C-Type; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D000099175:Heparanase; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002843:Chromatin; D005966:Glucuronidase; D006657:Histones; D006877:Hydroxamic Acids; D037181:Lectins, C-Type; D012319:RNA Polymerase II; D012333:RNA, Messenger; D000099175:Heparanase; D000099192:CD69 Antigens; C012589:trichostatin A