posted on 2023-03-31, 02:24authored byJoseph Castillo, Esther Wu, Christopher Lowe, Shrividhya Srinivasan, Ron McCord, Marie-Claire Wagle, Sangeeta Jayakar, Melissa Gonzalez Edick, Jeffrey Eastham-Anderson, Bonnie Liu, Katherine E. Hutchinson, Wendell Jones, Matthew P. Stokes, Somayeh S. Tarighat, Thomas Holcomb, Andrew Glibicky, F. Anthony Romero, Steven Magnuson, Shih-Min A. Huang, Vicki Plaks, Jennifer M. Giltnane, Mark R. Lackner, Zineb Mounir
<p>Supplementary table 1 shows the list of 2153 genes identified as the human Treg differentiation geneset. Supplementary table 2 shows the list of 2602 genes regulated by CBP/p300 bromodomain during Treg differentiation. Supplementary table 3 shows the list of 824 genes identified as Treg-specific CBP/p300 bromodomain-dependent geneset. Supplementary table 4 shows the list of 959 genes identified by H3K27Ac ChIPseq that are directly acetylated by CBP/p300 during Treg differentiation. Supplementary table 5 shows the list of 57 genes in the Treg-specific gene signature identified by combined analysis of H3K27Ac ChIPseq and RNAseq dataset analyses.</p>
Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of CBP/p300 loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring CBP/p300 loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape.
This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma.