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Cell Rep ; 25(7): 1729-1740.e6, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30428344

RESUMO

Tcrb locus V(D)J recombination is regulated by positioning at the nuclear periphery. Here, we used DamID to profile Tcrb locus interactions with the nuclear lamina at high resolution. We identified a lamina-associated domain (LAD) border composed of several CTCF-binding elements that segregates active non-LAD from inactive LAD regions of the locus. Deletion of the LAD border causes an enhancer-dependent spread of histone H3 lysine 27 acetylation from the active recombination center into recombination center-proximal LAD chromatin. This is associated with a disruption to nuclear lamina association, increased chromatin looping to the recombination center, and increased transcription and recombination of recombination center-proximal gene segments. Our results show that a LAD and LAD border are critical components of Tcrb locus gene regulation and suggest that LAD borders may generally function to constrain the activity of nearby enhancers.


Assuntos
Loci Gênicos , Lâmina Nuclear/metabolismo , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Recombinação Genética/genética , Transcrição Gênica , Animais , Linhagem Celular , Cromatina/metabolismo , Histonas/metabolismo , Humanos , Lisina/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Ativação Transcricional/genética , Recombinação V(D)J/genética
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