RESUMO
Lymphopoiesis requires the activation of lineage-specific genes embedded in naive, inaccessible chromatin or in primed, accessible chromatin. The mechanisms responsible for de novo gain of chromatin accessibility, known as "pioneer" function, remain poorly defined. Here, we showed that the EBF1 C-terminal domain (CTD) is required for the regulation of a specific gene set involved in B cell fate decision and differentiation, independently of activation and repression functions. Using genome-wide analysis of DNaseI hypersensitivity and DNA methylation in multipotent Ebf1(-/-) progenitors and derivative EBF1wt- or EBF1ΔC-expressing cells, we found that the CTD promoted chromatin accessibility and DNA demethylation in previously naive chromatin. The CTD allowed EBF1 to bind at inaccessible genomic regions that offer limited co-occupancy by other transcription factors, whereas the CTD was dispensable for EBF1 binding at regions that are occupied by multiple transcription factors. Thus, the CTD enables EBF1 to confer permissive lineage-specific changes in progenitor chromatin landscape.
Assuntos
Linfócitos B/fisiologia , Cromatina/metabolismo , Células Progenitoras Linfoides/fisiologia , Transativadores/metabolismo , Animais , Diferenciação Celular/genética , Linhagem da Célula/genética , Células Cultivadas , Metilação de DNA/genética , Redes Reguladoras de Genes/genética , Linfopoese , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Estrutura Terciária de Proteína/genética , Transativadores/genéticaRESUMO
The transcription factors EBF1 and Pax5 have been linked to activation of the B cell lineage program and irreversible loss of alternative lineage potential (commitment), respectively. Here we conditionally deleted Ebf1 in committed pro-B cells after transfer into alymphoid mice. We found that those cells converted into innate lymphoid cells (ILCs) and T cells with variable-diversity-joining (VDJ) rearrangements of loci encoding both B cell and T cell antigen receptors. As intermediates in lineage conversion, Ebf1-deficient CD19(+) cells expressing Pax5 and transcriptional regulators of the ILC and T cell fates were detectable. In particular, genes encoding the transcription factors Id2 and TCF-1 were bound and repressed by EBF1. Thus, both EBF1 and Pax5 are required for B lineage commitment by repressing distinct and common determinants of alternative cell fates.
Assuntos
Linfócitos B/imunologia , Transativadores/imunologia , Transferência Adotiva , Animais , Linfócitos B/citologia , Diferenciação Celular/imunologia , Linhagem da Célula , DNA/química , DNA/genética , Regulação da Expressão Gênica , Linfopoese/imunologia , Camundongos , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Transativadores/genética , Recombinação V(D)J/genética , Recombinação V(D)J/imunologiaRESUMO
The aim of this study is to assess the validity and reliability of a Turkish version of the Body Shape Questionnaire (BSQ) among young people. The BSQ was initially administrated to female high school students (N = 665) and administered a second time to a subset of subjects (N = 144). The subjects also completed the Eating Attitudes Test, the Body Image Satisfaction Questionnaire (a dieting questionnaire) and the Hopkins Symptom Checklist (SCL-90), and were weighed, and their body mass indices were calculated. Test-retest reliability of the BSQ was 0.81. The BSQ score correlated highly with the Eating Attitudes Test, Body Image Satisfaction Questionnaire and the Hopkins Symptom Checklist. Higher BSQ scores were also associated with higher body mass index. The results suggest that the Turkish version of BSQ is a valid and reliable tool for assessing body image concerns in teenagers.