The histone acetyltransferase KAT6B is required for hematopoietic stem cell development and function

Bergamasco, MI; Ranathunga, N; Abeysekera, W; Li-Wai-Suen, CSN; Garnham, AL; Willis, SN; McRae, HM; Yang, Y; D&#39;Amico, A; Di Rago, L; Wilcox, S; Nutt, SL; Alexander, WS; Smyth, GK; Voss, AK; Thomas, T

Author(s): Bergamasco, MI; Ranathunga, N; Abeysekera, W; Li-Wai-Suen, CSN; Garnham, AL; Willis, SN; McRae, HM; Yang, Y; D'Amico, A; Di Rago, L; Wilcox, S; Nutt, SL; Alexander, WS; Smyth, GK; Voss, AK; Thomas, T;
Details: Publication Year 2024-03-11,Volume 19,Issue #4,Page 469-485
Journal Title: Stem Cell Reports
Abstract: The histone lysine acetyltransferase KAT6B (MYST4, MORF, QKF) is the target of recurrent chromosomal translocations causing hematological malignancies with poor prognosis. Using Kat6b germline deletion and overexpression in mice, we determined the role of KAT6B in the hematopoietic system. We found that KAT6B sustained the fetal hematopoietic stem cell pool but did not affect viability or differentiation. KAT6B was essential for normal levels of histone H3 lysine 9 (H3K9) acetylation but not for a previously proposed target, H3K23. Compound heterozygosity of Kat6b and the closely related gene, Kat6a, abolished hematopoietic reconstitution after transplantation. KAT6B and KAT6A cooperatively promoted transcription of genes regulating hematopoiesis, including the Hoxa cluster, Pbx1, Meis1, Gata family, Erg, and Flt3. In conclusion, we identified the hematopoietic processes requiring Kat6b and showed that KAT6B and KAT6A synergistically promoted HSC development, function, and transcription. Our findings are pertinent to current clinical trials testing KAT6A/B inhibitors as cancer therapeutics.
Publisher: Elsevier
Keywords: Kat6a; Kat6b; chromatin; hematopoiesis; histone acetyltransferase; stem cells; transplantation
Research Division(s): Advanced Technology And Biology; Bioinformatics; Blood Cells And Blood Cancer; Immunology; Epigenetics And Development; Bioinformatics; Immunology; Advanced Technology and Biology; Blood Cells and Blood Cancer
PubMed ID: 38518784
Publisher's Version: https://doi.org/10.1016/j.stemcr.2024.02.005
Open Access at Publisher's Site: https://doi.org/10.1016/j.stemcr.2024.02.005
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-03-27 08:35:38

Last Modified: 2024-06-28 03:08:43