The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis

Area of Science:

• Cell Biology
• Molecular Biology
• Epigenetics

Background:

• Somatic cell nuclear transfer (SCNT) is a reprogramming technique where both recipient cells and donor nuclei show a mitotic advantage.
• The specific molecular mechanisms and factors driving this mitotic advantage in reprogramming remain largely unknown.

Purpose of the Study:

• To identify specific mitotic factors crucial for the reprogramming process.
• To elucidate the role of these factors in regulating mitosis and gene expression during reprogramming.

Main Methods:

• Identification and characterization of BRD3R (BRD3 with Reprogramming activity), an isoform of human bromodomain-containing 3 (BRD3).
• Analysis of BRD3R's effect on mitosis, gene expression (particularly mitotic genes), and chromatin association during reprogramming.
• Investigation of differential histone binding between BRD3 isoforms.

Main Results:

• BRD3R was identified as a key reprogramming factor that positively regulates mitosis.
• BRD3R upregulates a significant number of mitotic genes early in reprogramming, many of which are linked to pluripotency.
• BRD3R associates with mitotic chromatin, and its isoforms show distinct binding to acetylated histones.

Conclusions:

• Mitosis may serve as a driving force in the reprogramming process.
• BRD3R provides a molecular explanation for the observed mitotic advantage in reprogramming.
• BRD3R's regulation of mitotic genes contributes to establishing a pluripotent molecular signature.