THE ALTERNATIVE SPLICING OF NF-YA REGULATES MOUSE EMBRYONIC STEM CELLS DIFFERENTIATION
type: CreativeWork
description: Embryogenesis is governed by a fine balance between pluripotency and differentiation controlled by a handful of Transcription Factors (TFs). Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation.
abstract: Embryogenesis is governed by a fine balance between pluripotency and differentiation controlled by a handful of Transcription Factors (TFs). Some are implied in the maintenance of self-renewal and pluripotency of Embryonic Stem Cells (ESC), others drive cell lineage decisions which give rise to the entire organism. An example of these factors is NF-Y, a heterotrimeric pioneer TF promoting chromatin accessibility to other TFs to regulate gene expression. The regulatory subunit of NF-Y, NF-YA, recognizes and binds the CCAAT box motif, one of the most enriched DNA elements in enhancers and promoters of genes specifically active in ESCs. NF-YA exists in two different isoforms generated by Alternative Splicing of Exon 3. The short (NF-YAs) and the long (NF-YAl) isoforms differ from a stretch of 28-29 amino acids in the N-terminal Q-rich activation domain. Although they display identical DNA-binding properties in vitro, the two isoforms have distinct roles in several biological processes. Regarding embryogenesis, NF-YAs is the predominant isoform in undifferentiated mouse ESCs, being crucial for the regulation of pluripotency and stemness maintenance. By contrast, during Embryoid Bodies (EB) formation process, NF-YAl prevails, suggesting an implication of this specific isoform in the differentiation of mESCs. Our data strengthen the stem-related function of NF-YAs and propose a novel role of NF-YAl in mesoderm formation to shed light on the distinct functions of NF-YA isoforms in the equilibrium between pluripotency and differentiation.
author: POLETTINI, SOFIA
language: eng
keywords: NF-Y, differentiation, embryoid bodies, mESCs, transcription factors, pluripotency, primitive streak, mesoderm., Settore BIOS-14/A - Genetica
date published: 2025-04-17
date modified: 2026-07-27T20:19:08Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1159559