AUTHOR=Cortés-Fernández de Lara Josué , Núñez-Martínez Hober Nelson , Tapia-Urzúa Gustavo , Garza-Manero Sylvia , Peralta-Alvarez Carlos Alberto , Furlan-Magaril Mayra , González-Buendía Edgar , Escamilla-Del-Arenal Martín , Casasola Andrea , Guerrero Georgina , Recillas-Targa Felix 

TITLE=A novel cis-regulatory element regulates αD and αA-globin gene expression in chicken erythroid cells

JOURNAL=Frontiers in Genetics

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1384167

DOI=10.3389/fgene.2024.1384167

ISSN=1664-8021

ABSTRACT=Cis-regulatory elements (CREs) are key players in erythroid cell differentiation. In this work, we compared genome-wide chromatin accessibility between proerythroblasts (HD3) and embryonic fibroblasts and we identified a novel erythroid-specific intergenic cis-regulatory element, which we refer to as CRE-2, embedded in the chicken α-globin loci. CRE-2 was enriched in active enhancer-associated histone marks throughout terminal erythroid differentiation. Using UMI-4C, we observed that CRE-2 is located within an interacting region encompassing the α-globin genes. By CRISPR-Cas9-mediated genomic editing, we deleted the CRE-2 in HD3 cells and observed that CRE-2 is required for proper αD and αAgene expression in HD3 cells and upon differentiation. Our findings demonstrate that cell-specific CREs contribute to the fine-tuning regulation of erythroid cell-specific genes.