title: Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation.
abstract: Somatic hypermutation (SHM) requires not only the expression of activation-induced cytidine deaminase, but also transcription in the target regions. However, how transcription guides activation-induced cytidine deaminase in targeting SHM to the Ig genes is not fully understood. Here, we found that the "facilitates chromatin transcription" (FACT) complex promotes SHM by RNAi screening of transcription elongation factors. Furthermore, FACT and histone H3.3, a hallmark of transcription-coupled histone turnover, are enriched at the V(D)J region, 5' flanking sequence of the Sμ switch region and the light chain Jκ 5 segment region in the Ig loci. The regions with the most abundant deposition of FACT and H3.3 were also the most efficient targets of SHM. These results demonstrate the importance of histone-exchanging dynamics at the chromatin of SHM targets, especially in Ig genes.
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Aida
authors.forename: Nesreen
authors.initials: N
authors.lastname: Hamad
authors.forename: Andre
authors.initials: A
authors.lastname: Stanlie
authors.forename: Nasim A
authors.initials: NA
authors.lastname: Begum
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D002934:Cinnamates / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D005819:Genetic Markers; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics*; D006801:Humans; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D007136:Immunoglobulins / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017422:Sequence Analysis, DNA; D027041:Somatic Hypermutation, Immunoglobulin; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000235:genetics / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D002843:Chromatin; D002934:Cinnamates; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006609:High Mobility Group Proteins; D006657:Histones; D007136:Immunoglobulins; D034741:RNA, Small Interfering; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors; D049452:Green Fluorescent Proteins; D006921:Hygromycin B; C026273:hygromycin A; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; SSRP1