Transformation of Accessible Chromatin and 3D Nucleome Underlies Lineage Commitment of Early T Cells.
Immunity
; 48(2): 227-242.e8, 2018 02 20.
Article
em En
| MEDLINE
| ID: mdl-29466755
ABSTRACT
How chromatin reorganization coordinates differentiation and lineage commitment from hematopoietic stem and progenitor cells (HSPCs) to mature immune cells has not been well understood. Here, we carried out an integrative analysis of chromatin accessibility, topologically associating domains, AB compartments, and gene expression from HSPCs to CD4+CD8+ T cells. We found that abrupt genome-wide changes at all three levels of chromatin organization occur during the transition from double-negative stage 2 (DN2) to DN3, accompanying the T lineage commitment. The transcription factor BCL11B, a critical regulator of T cell commitment, is associated with increased chromatin interaction, and Bcl11b deletion compromised chromatin interaction at its target genes. We propose that these large-scale and concerted changes in chromatin organization present an energy barrier to prevent the cell from reversing its fate to earlier stages or redirecting to alternatives and thus lock the cell fate into the T lineages.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cromatina
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Linfócitos T
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Núcleo Celular
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Linhagem da Célula
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article