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Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis

(2021) IMMUNITY. 54(7). p.1417-1432.e7
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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.
Keywords
Immunology, Immunology and Allergy, Infectious Diseases, SMAD-INTERACTING PROTEIN-1, PERIPHERAL LYMPHOID ORGANS, DENDRITIC CELL, YOLK-SAC, TERMINAL DIFFERENTIATION, PHENOTYPIC ROBUSTNESS, MYELOID PROGENITORS, FETAL LIVER, IN-VITRO, T-BET

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MLA
Huang, Xiao, et al. “Differential Usage of Transcriptional Repressor Zeb2 Enhancers Distinguishes Adult and Embryonic Hematopoiesis.” IMMUNITY, vol. 54, no. 7, 2021, pp. 1417-1432.e7, doi:10.1016/j.immuni.2021.04.015.
APA
Huang, X., Ferris, S. T., Kim, S., Choudhary, M. N. K., Belk, J. A., Fan, C., … Murphy, K. M. (2021). Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis. IMMUNITY, 54(7), 1417-1432.e7. https://doi.org/10.1016/j.immuni.2021.04.015
Chicago author-date
Huang, Xiao, Stephen T. Ferris, Sunkyung Kim, Mayank N.K. Choudhary, Julia A. Belk, Changxu Fan, Yanyan Qi, et al. 2021. “Differential Usage of Transcriptional Repressor Zeb2 Enhancers Distinguishes Adult and Embryonic Hematopoiesis.” IMMUNITY 54 (7): 1417-1432.e7. https://doi.org/10.1016/j.immuni.2021.04.015.
Chicago author-date (all authors)
Huang, Xiao, Stephen T. Ferris, Sunkyung Kim, Mayank N.K. Choudhary, Julia A. Belk, Changxu Fan, Yanyan Qi, Raki Sudan, Yu Xia, Pritesh Desai, Jing Chen, Nghi Ly, Quanming Shi, Prachi Bagadia, Tiantian Liu, Martin Guilliams, Takeshi Egawa, Marco Colonna, Michael S. Diamond, Theresa L. Murphy, Ansuman T. Satpathy, Ting Wang, and Kenneth M. Murphy. 2021. “Differential Usage of Transcriptional Repressor Zeb2 Enhancers Distinguishes Adult and Embryonic Hematopoiesis.” IMMUNITY 54 (7): 1417-1432.e7. doi:10.1016/j.immuni.2021.04.015.
Vancouver
1.
Huang X, Ferris ST, Kim S, Choudhary MNK, Belk JA, Fan C, et al. Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis. IMMUNITY. 2021;54(7):1417-1432.e7.
IEEE
[1]
X. Huang et al., “Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis,” IMMUNITY, vol. 54, no. 7, pp. 1417-1432.e7, 2021.
@article{8712075,
  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.}},
  author       = {{Huang, Xiao and Ferris, Stephen T. and Kim, Sunkyung and Choudhary, Mayank N.K. and Belk, Julia A. and Fan, Changxu and Qi, Yanyan and Sudan, Raki and Xia, Yu and Desai, Pritesh and Chen, Jing and Ly, Nghi and Shi, Quanming and Bagadia, Prachi and Liu, Tiantian and Guilliams, Martin and Egawa, Takeshi and Colonna, Marco and Diamond, Michael S. and Murphy, Theresa L. and Satpathy, Ansuman T. and Wang, Ting and Murphy, Kenneth M.}},
  issn         = {{1074-7613}},
  journal      = {{IMMUNITY}},
  keywords     = {{Immunology,Immunology and Allergy,Infectious Diseases,SMAD-INTERACTING PROTEIN-1,PERIPHERAL LYMPHOID ORGANS,DENDRITIC CELL,YOLK-SAC,TERMINAL DIFFERENTIATION,PHENOTYPIC ROBUSTNESS,MYELOID PROGENITORS,FETAL LIVER,IN-VITRO,T-BET}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1417--1432.e7}},
  title        = {{Differential usage of transcriptional repressor Zeb2 enhancers distinguishes adult and embryonic hematopoiesis}},
  url          = {{http://dx.doi.org/10.1016/j.immuni.2021.04.015}},
  volume       = {{54}},
  year         = {{2021}},
}

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