title: Tissue-specific inactivation of HAT cofactor TRRAP reveals its essential role in B cells.
abstract: The transformation/transcription domain-associated protein (TRRAP) is a common component of many histone acetyltransferase (HAT) complexes. Targeted-deletion of the Trrap gene led to early embryonic lethality and revealed a critical function of TRRAP in cell proliferation. Here, we investigate the function of TRRAP in murine B cells. To this end, we ablated Trrap gene in a B cell-restricted manner and studied its impact on B-cell development and proliferation, a pre-requisite for class switch recombination (CSR), the process that allows IgM-expressing B lymphocytes to switch to the expression of IgG, IgE, or IgA isotypes. We show that TRRAP deficiency impairs B-cell development but does not directly affect CSR. Instead, cells induced to proliferate undergo apoptosis. Our findings demonstrate a central and general role of TRRAP in cell proliferation.
authors.affiliation: CNRS UMR5089; IPBS (Institut de Pharmacologie et de Biologie Structurale); Toulouse, France; Université de Toulouse; UPS; IPBS; Toulouse, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Leduc
authors.affiliation: CNRS UMR5089; IPBS (Institut de Pharmacologie et de Biologie Structurale); Toulouse, France; Université de Toulouse; UPS; IPBS; Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Chemin
authors.affiliation: CNRS UMR5089; IPBS (Institut de Pharmacologie et de Biologie Structurale); Toulouse, France; Université de Toulouse; UPS; IPBS; Toulouse, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Puget
authors.affiliation: International Agency for Research on Cancer (IARC); Lyon, France.
authors.forename: Carla
authors.initials: C
authors.lastname: Sawan
authors.affiliation: CNRS UMR5089; IPBS (Institut de Pharmacologie et de Biologie Structurale); Toulouse, France; Université de Toulouse; UPS; IPBS; Toulouse, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Moutahir
authors.affiliation: International Agency for Research on Cancer (IARC); Lyon, France.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
authors.affiliation: CNRS UMR5089; IPBS (Institut de Pharmacologie et de Biologie Structurale); Toulouse, France; Université de Toulouse; UPS; IPBS; Toulouse, France.
authors.forename: Ahmed Amine
authors.initials: AA
authors.lastname: Khamlichi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D051548:Histone Acetyltransferases / Q000378:metabolism*; D017578:Immunoglobulin Class Switching; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009687:Nuclear Proteins; C113829:transformation-transcription domain-associated protein; D051548:Histone Acetyltransferases
keywords: B lymphocyte; TRRAP; class switch recombination; immunoglobulin gene; proliferation