EBF1 is continuously required for stabilizing local chromatin accessibility in pro-B cells.

Area of Science:

• Epigenetics
• Molecular Biology
• Developmental Biology

Background:

• Early B cell factor 1 (EBF1) is a pioneering transcription factor essential for establishing chromatin accessibility in lymphoid progenitors.
• EBF1 recruits the BRG1 chromatin remodeler to induce accessibility at naïve chromatin.

Purpose of the Study:

• To investigate whether the function of EBF1 is continuously required for stabilizing local chromatin accessibility in pro-B cells.
• To determine the impact of EBF1 degradation on genome-wide occupancy, chromatin accessibility, and gene expression.

Main Methods:

• Utilized a degron system by replacing endogenous EBF1 with EBF1-FKBP^F36V in pro-B cells.
• Administered the degradation TAG13 (dTAG13) dimerizer to induce rapid EBF1 degradation.
• Assessed genome-wide EBF1 occupancy, BRG1 binding, chromatin accessibility, and gene expression changes post-EBF1 degradation.

Main Results:

• EBF1 degradation led to a rapid loss of genome-wide EBF1 occupancy and EBF1-targeted BRG1 binding.
• Chromatin accessibility significantly diminished at EBF1-binding sites, particularly those dependent on the EBF1 C-terminal domain.
• Decreased chromatin accessibility correlated with significant alterations in gene expression patterns.

Conclusions:

• Continuous EBF1 activity is essential for the stable maintenance of chromatin accessibility in pro-B cells.
• EBF1 plays a sustained role in preserving the transcriptional and epigenetic state of developing B cells.
• The pioneering function of EBF1 is not only required for initiation but also for the ongoing stabilization of chromatin accessibility.