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 (Dot1l-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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.813503/full |
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| author | Carrie A. Malcom Anamika Ratri Joanna Piasecka-Srader Shaon Borosha V. Praveen Chakravarthi Nehemiah S. Alvarez Jay L. Vivian Timothy A. Fields M.A. Karim Rumi Patrick E. Fields |
| author_facet | Carrie A. Malcom Anamika Ratri Joanna Piasecka-Srader Shaon Borosha V. Praveen Chakravarthi Nehemiah S. Alvarez Jay L. Vivian Timothy A. Fields M.A. Karim Rumi Patrick E. Fields |
| author_sort | Carrie A. Malcom |
| collection | DOAJ |
| description | DOT1-like (DOT1L) histone methyltransferase is essential for mammalian erythropoiesis. Loss of DOT1L in knockout (Dot1l-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 Dot1l methyltransferase mutant (Dot1l-MM) mouse model to determine the role of DOT1L methyltransferase activity in early embryonic hematopoiesis. Dot1l-MM embryos failed to survive beyond embryonic day 13.5 (E13.5), similarly to Dot1l-KO mice. However, when examined at E10.5, Dot1l-MM embryos did not exhibit overt anemia like the Dot1l-KO. Vascularity and the presence of red blood cells in the Dot1l-MM yolk sacs as well as in the AGM region of Dot1l-MM embryos appeared to be similar to that of wildtype. In ex vivo cultures of yolk sac cells, Dot1l-MM primitive erythroblasts formed colonies comparable to those of the wildtype. Although ex vivo cultures of Dot1l-MM definitive erythroblasts formed relatively smaller colonies, inhibition of DOT1L methyltransferase activity in vivo 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. |
| first_indexed | 2024-04-11T18:23:24Z |
| format | Article |
| id | doaj.art-9d02827bb57c496bb59d86a36e15f936 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-11T18:23:24Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-9d02827bb57c496bb59d86a36e15f9362022-12-22T04:09:43ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-01-01910.3389/fcell.2021.813503813503Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase ActivityCarrie A. MalcomAnamika RatriJoanna Piasecka-SraderShaon BoroshaV. Praveen ChakravarthiNehemiah S. AlvarezJay L. VivianTimothy A. FieldsM.A. Karim RumiPatrick E. FieldsDOT1-like (DOT1L) histone methyltransferase is essential for mammalian erythropoiesis. Loss of DOT1L in knockout (Dot1l-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 Dot1l methyltransferase mutant (Dot1l-MM) mouse model to determine the role of DOT1L methyltransferase activity in early embryonic hematopoiesis. Dot1l-MM embryos failed to survive beyond embryonic day 13.5 (E13.5), similarly to Dot1l-KO mice. However, when examined at E10.5, Dot1l-MM embryos did not exhibit overt anemia like the Dot1l-KO. Vascularity and the presence of red blood cells in the Dot1l-MM yolk sacs as well as in the AGM region of Dot1l-MM embryos appeared to be similar to that of wildtype. In ex vivo cultures of yolk sac cells, Dot1l-MM primitive erythroblasts formed colonies comparable to those of the wildtype. Although ex vivo cultures of Dot1l-MM definitive erythroblasts formed relatively smaller colonies, inhibition of DOT1L methyltransferase activity in vivo 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.813503/fullDOT1L methyltransferaseDot1l methyltransferase mutant mouseerythroid progenitorerythroid differentiationearly blood development |
| spellingShingle | Carrie A. Malcom Anamika Ratri Joanna Piasecka-Srader Shaon Borosha V. Praveen Chakravarthi Nehemiah S. Alvarez Jay L. Vivian Timothy A. Fields M.A. Karim Rumi Patrick E. Fields Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity Frontiers in Cell and Developmental Biology DOT1L methyltransferase Dot1l methyltransferase mutant mouse erythroid progenitor erythroid differentiation early blood development |
| title | Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity |
| title_full | Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity |
| title_fullStr | Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity |
| title_full_unstemmed | Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity |
| title_short | Primitive Erythropoiesis in the Mouse is Independent of DOT1L Methyltransferase Activity |
| title_sort | primitive erythropoiesis in the mouse is independent of dot1l methyltransferase activity |
| topic | DOT1L methyltransferase Dot1l methyltransferase mutant mouse erythroid progenitor erythroid differentiation early blood development |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.813503/full |
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