title: Divergence of transcriptional landscape occurs early in B cell activation.
abstract: BACKGROUND
  Signaling via B cell receptor (BCR) and Toll-like receptors (TLRs) results in activation of B cells with distinct physiological outcomes, but transcriptional regulatory mechanisms that drive activation and distinguish these pathways remain unknown.
  
  
  RESULTS
  Two hours after ligand exposure RNA-seq, ChIP-seq and computational methods reveal that BCR- or TLR-mediated activation of primary resting B cells proceeds via a large set of shared and a smaller subset of distinct signal-selective transcriptional responses. BCR stimulation resulted in increased global recruitment of RNA Pol II to promoters that appear to transit slowly to downstream regions. Conversely, lipopolysaccharide (LPS) stimulation involved an enhanced RNA Pol II transition from initiating to elongating mode accompanied by greater H3K4me3 activation markings compared to BCR stimulation. These rapidly diverging transcriptomic landscapes also show distinct repressing (H3K27me3) histone signatures, mutually exclusive transcription factor binding in promoters, and unique miRNA profiles.
  
  
  CONCLUSIONS
  Upon examination of genome-wide transcription and regulatory elements, we conclude that the B cell commitment to different activation states occurs much earlier than previously thought and involves a multi-faceted receptor-specific transcriptional landscape.
authors.affiliation: Department of Developmental, Chemical and Molecular Biology, Sackler School of Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111 USA.
authors.forename: Trent
authors.initials: T
authors.lastname: Fowler
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University and Department of Genetics, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Garruss
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224 USA.
authors.forename: Amalendu
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224 USA ; Gene Expression Unit, Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224 USA.
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224 USA ; Gene Expression Unit, Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224 USA.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224 USA ; Gene Expression Unit, Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224 USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.affiliation: Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Weirauch
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095 USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smale
authors.affiliation: Center for Autoimmune Genomics and Etiology (CAGE) and Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229 USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Aronow
authors.affiliation: Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224 USA.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Sen
authors.affiliation: Department of Developmental, Chemical and Molecular Biology, Sackler School of Biomedical Science, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111 USA.
authors.forename: Ananda L
authors.initials: AL
authors.lastname: Roy