A conserved element in the first intron of <i>Cd4</i> has a lineage specific, TCR signal-responsive, canonical enhancer function that matches the timing of cell surface CD4 upregulation required to prevent lineage choice error.

ABSTRACT:

Introduction

The regulation of Cd4 expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage. In this study, we investigate whether a conserved region, here called NCE, that is proximal to the Cd4 silencer and contains E4m has the required developmental-stage-specific canonical enhancer function and TCR responsiveness to mediate the CD4 upregulation required to prevent lineage errors.

Methods

To investigate the role of

SUBMITTER: Swan GA 

PROVIDER: S-EPMC11774700 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature