title: Mice lacking Sμ tandem repeats maintain RNA polymerase patterns but exhibit histone modification pattern shifts linked to class switch site locations.
abstract: Antibody switching involves class switch recombination (CSR) events between switch (S) regions located upstream of heavy chain constant (C) genes. Mechanisms targeting CSR to S-regions are not clear. Deletion of Sμ tandem repeat (SμTR) sequences causes CSR to shift into downstream regions that do not undergo CSR in WT B-cells, including the Cμ-region. We now find that, in SμTR(-/-) B cells, Sμ chromatin histone modification patterns also shift downstream relative to WT and coincide with SμTR(-/-) CSR locations. Our results suggest that histone H3 acetylation and methylation are involved in accessibility of switch regions and that these modifications are not dependent on the underlying sequence, but may be controlled by the location of upstream promoter or regulatory elements. Our studies also show RNA polymerase II (RNAPII) loading increases in the Eμ/Iμ region in stimulated B cells; these increases are independent of SμTR sequences. Longer Sμ deletions have been reported to eliminate increases in RNAPII density, therefore we suggest that sequences between Iμ and Sμ (possibly the Iμ splicing region as well as G-tracts that are involved in stable RNA:DNA complex formation during transcription) might control the RNAPII density increases.
authors.affiliation: Immunology Program and Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Balter
authors.forename: David N
authors.initials: DN
authors.lastname: Ciccone
authors.forename: Marjorie A
authors.initials: MA
authors.lastname: Oettinger
authors.forename: Erik
authors.initials: E
authors.lastname: Selsing
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000276:immunology; D053960:DNA Breaks; D055786:Gene Knockout Techniques; D006657:Histones / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences
chemical_list: D006657:Histones; D007148:Immunoglobulin mu-Chains; D012319:RNA Polymerase II