Histone acetyltransferase activity of MOF is required for adult but not early fetal hematopoiesis in mice.
K(lysine) acetyltransferase 8 (KAT8, also known as MOF) mediates the acetylation of histone H4 at lysine 16 (H4K16ac) and is crucial for murine embryogenesis. Lysine acetyltransferases have been shown to regulate various stages of normal hematopoiesis. However, the function of MOF in hematopoietic stem cell (HSC) development has not yet been elucidated. We set out to study the role of MOF in general hematopoiesis by using a Vav1-cre-induced conditional murine Mof knockout system and found that MOF is critical for hematopoietic cell maintenance and HSC engraftment capacity in adult hematopoiesis. Rescue experiments with a MOF histone acetyltransferase domain mutant illustrated the requirement for MOF acetyltransferase activity in the clonogenic capacity of HSCs and progenitors. In stark contrast, fetal steady-state hematopoiesis at embryonic day (E) 14.5 was not affected by homozygous Mof deletion despite dramatic loss of global H4K16ac. Hematopoietic defects start manifesting in late gestation at E17.5. The discovery that MOF and its H4K16ac activity are required for adult but not early and midgestational hematopoiesis supports the notion that multiple chromatin regulators may be crucial for hematopoiesis at varying stages of development. MOF is therefore a developmental-stage-specific chromatin regulator found to be essential for adult but not early fetal hematopoiesis.
Center for Epigenetics Research, and.|Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Daria G
DG
Valerio
Center for Epigenetics Research, and.|Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Haiming
H
Xu
Center for Epigenetics Research, and.|Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Meghan E
ME
Eisold
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Carolien M
CM
Woolthuis
Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX; and.
Tej K
TK
Pandita
Center for Epigenetics Research, and.|Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.|Department of Pediatric Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Scott A
SA
Armstrong
D000818:Animals; D005333:Fetus; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D051548:Histone Acetyltransferases; C000622683:Kat8 protein, mouse