| Literature DB >> 34004142 |
Xiao Huang1, Stephen T Ferris1, Sunkyung Kim1, Mayank N K Choudhary2, Julia A Belk3, Changxu Fan2, Yanyan Qi4, Raki Sudan1, Yu Xia1, Pritesh Desai5, Jing Chen1, Nghi Ly4, Quanming Shi4, Prachi Bagadia6, Tiantian Liu1, Martin Guilliams7, Takeshi Egawa1, Marco Colonna1, Michael S Diamond8, Theresa L Murphy1, Ansuman T Satpathy4, Ting Wang9, Kenneth M Murphy10.
Abstract
The transcriptional repressor ZEB2 regulates development of many cell fates among somatic, neural, and hematopoietic lineages, but the basis for its requirement in these diverse lineages is unclear. Here, we identified a 400-basepair (bp) region located 165 kilobases (kb) upstream of the Zeb2 transcriptional start site (TSS) that binds the E proteins at several E-box motifs and was active in hematopoietic lineages. Germline deletion of this 400-bp region (Zeb2Δ-165mice) specifically prevented Zeb2 expression in hematopoietic stem cell (HSC)-derived lineages. Zeb2Δ-165 mice lacked development of plasmacytoid dendritic cells (pDCs), monocytes, and B cells. All macrophages in Zeb2Δ-165 mice were exclusively of embryonic origin. Using single-cell chromatin profiling, we identified a second Zeb2 enhancer located at +164-kb that was selectively active in embryonically derived lineages, but not HSC-derived ones. Thus, Zeb2 expression in adult, but not embryonic, hematopoiesis is selectively controlled by the -165-kb Zeb2 enhancer.Entities:
Keywords: Zeb2; chromatin structure; enhancer; hematopoiesis; transcriptional regulation; zinc finger E-box binding homeobox 2
Mesh：
Substances：
Year: 2021 PMID： 34004142 PMCID： PMC8282756 DOI： 10.1016/j.immuni.2021.04.015
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 43.474