TitleDNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation.
Publication TypeJournal Article
Year of Publication2013
AuthorsLai, Anne Y., Mav Deepak, Shah Ruchir, Grimm Sara A., Phadke Dhiral, Hatzi Katerina, Melnick Ari, Geigerman Cissy, Sobol Steve E., Jaye David L., and Wade Paul A.
JournalGenome Res
Volume23
Issue12
Pagination2030-41
Date Published2013 Dec
ISSN1549-5469
KeywordsAdaptive Immunity, Alu Elements, B-Lymphocytes, Binding Sites, Cell Differentiation, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, DNA Methyltransferase 3A, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, Humans, Immunologic Memory, Lymphocyte Activation, Plasma Cells, Regulatory Elements, Transcriptional, Transcription Factors
Abstract

<p>Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.</p>

DOI10.1101/gr.155473.113
Alternate JournalGenome Res
PubMed ID24013550
PubMed Central IDPMC3847773
Grant ListZ01 ES101965 / / Intramural NIH HHS / United States
DK60647 / DK / NIDDK NIH HHS / United States
Z01ES101965 / ES / NIEHS NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
K08 DK060647 / DK / NIDDK NIH HHS / United States
HHSN291200555547 / / PHS HHS / United States