title: Epigenetic regulation of CIITA expression in human T-cells.
abstract: In humans, T-cells accomplish expression of MHC-II molecules through induction of CIITA upon activation. Here we show that CIITA promoter accessibility in T-cells is epigenetically regulated. In unstimulated T-cells, CIITA-PIII chromatin displays relative high levels of repressive histone methylation marks (3Me-K27-H3 and 3Me-K20-H4) and low levels of acetylated histones H3 (Ac-H3) and H4 (Ac-H4). These repressive histone marks are replaced by histone methylation marks associated with transcriptional active genes (3Me-K4-H3) and high levels of Ac-H3 and Ac-H4 in activated T-cells. This is associated with concomitant recruitment of RNA polymerase II. In T-leukemia cells, devoid of CIITA expression, similar repressive histone methylation marks and low levels of acetylated histone H3 correlated with lack of CIITA expression. This in contrast to CIITA expressing T-lymphoma cells, which display high levels of Ac-H3 and 3Me-K4-H3, and relative low levels of the 3Me-K27-H3 and 3Me-K20-H4 marks. Of interest was the observation that the levels of histone acetylation and methylation modifications in histones H3 and H4 were also noted in chromatin of the downstream CIITA-PIV promoter as well as the upstream CIITA-PI and CIITA-PII promoters both in normal T-cells and in malignant T-cells. Together our data show that CIITA chromatin in T-cells expressing CIITA display similar histone acetylation and methylation characteristics associated with an open chromatin structure. The opposite is true for T-cells lacking CIITA expression, which display histone modifications characteristic of condensed chromatin.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marja C J A
authors.initials: MC
authors.lastname: van Eggermond
authors.forename: Daniël R
authors.initials: DR
authors.lastname: Boom
authors.forename: Petra
authors.initials: P
authors.lastname: Klous
authors.forename: Erik
authors.initials: E
authors.lastname: Schooten
authors.forename: Victor E
authors.initials: VE
authors.lastname: Marquez
authors.forename: Rutger J
authors.initials: RJ
authors.lastname: Wierda
authors.forename: Tjadine M
authors.initials: TM
authors.lastname: Holling
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators