Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity

DOT1-like (DOT1L) histone methyltransferase is essential for mammalian erythropoiesis. Loss of DOT1L in knockout ( KO) mouse embryos resulted in lethal anemia at midgestational age. The only recognized molecular function of DOT1L is its methylation of histone H3 lysine 79 (H3K79). We generated a met...

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Published inFrontiers in cell and developmental biology Vol. 9; p. 813503
Main Authors Malcom, Carrie A, Ratri, Anamika, Piasecka-Srader, Joanna, Borosha, Shaon, Chakravarthi, V Praveen, Alvarez, Nehemiah S, Vivian, Jay L, Fields, Timothy A, Karim Rumi, M A, Fields, Patrick E
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 17.01.2022
Subjects
Cell and Developmental Biology
DOT1L methyltransferase
Dot1l methyltransferase mutant mouse
early blood development
erythroid differentiation
erythroid progenitor
early blood development
erythroid progenitor
DOT1L methyltransferase
Dot1l methyltransferase mutant mouse
erythroid differentiation
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Summary:DOT1-like (DOT1L) histone methyltransferase is essential for mammalian erythropoiesis. Loss of DOT1L in knockout ( KO) mouse embryos resulted in lethal anemia at midgestational age. The only recognized molecular function of DOT1L is its methylation of histone H3 lysine 79 (H3K79). We generated a methyltransferase mutant ( ) mouse model to determine the role of DOT1L methyltransferase activity in early embryonic hematopoiesis. embryos failed to survive beyond embryonic day 13.5 (E13.5), similarly to KO mice. However, when examined at E10.5, embryos did not exhibit overt anemia like the . Vascularity and the presence of red blood cells in the yolk sacs as well as in the AGM region of embryos appeared to be similar to that of wildtype. In cultures of yolk sac cells, primitive erythroblasts formed colonies comparable to those of the wildtype. Although cultures of definitive erythroblasts formed relatively smaller colonies, inhibition of DOT1L methyltransferase activity by administration of EPZ-5676 minimally affected the erythropoiesis. Our results indicate that early embryonic erythropoiesis in mammals requires a DOT1L function that is independent of its intrinsic methyltransferase activity.
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Reviewed by: Hengbin Wang, University of Alabama at Birmingham, United States
These authors have contributed equally to this work
Jorg Bungert, University of Florida, United States
This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Cell and Developmental Biology
Edited by: Tamer Onder, Koç University, Turkey
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2021.813503