Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7

Kueh, Andrew J.; Bergamasco, Maria Isabella; Quaglieri, Anna; Phipson, Belinda; Suen, Connie S. N. Li Wai; Lönnstedt, Ingrid; Hu, Yifang; Feng, Zhiping; Woodruff, Chris; May, Rose E.; Wilcox, Stephen; Garnham, Alexandra L.; Snyder, M; Smyth, Gordon K.; Speed, Terence P.; Thomas, Tim; Voss, Anne

doi:10.1016/j.celrep.2022.111980

Cited by 6 publications

(6 citation statements)

References 97 publications

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“…In other studies, KAT6B has been shown to acetylate H3K23 in small cell lung cancer cells ( Simo-Riudalbas et al., 2015 ) and K562 and 293T cell lines ( Klein et al., 2019 ), with no effect on H3K9ac or H3K14ac described. KAT7, by comparison, is required for global H3K14ac levels in a variety of cell types ( Kueh et al., 2011 , 2023 ), while KAT6A has been shown to be required for H3K9ac in vivo at specific loci ( Voss et al., 2009 , 2012 ) and H3K23 in glioblastoma cell lines in vitro ( Lv et al., 2017 ). Consistently, we observed a global reduction in H3K23ac in Kat6a +/− fetal liver cells and reduction in both H3K9ac and H3K23ac when both KAT6B and KAT6A were deficient.…”

Section: Discussionmentioning

confidence: 99%

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

Bergamasco,

Ranathunga,

Abeysekera

et al. 2024

Stem Cell Reports

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Section: Discussionmentioning

confidence: 99%

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

Bergamasco,

Ranathunga,

Abeysekera

et al. 2024

Stem Cell Reports

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“…This suggests that ING5 has a specific role in modulating the activity of chromatin regulatory complexes in which it is found. KAT7 has a global function in regulating H3K14ac ( 46 , 60 – 62 ), but under different conditions has been shown to acetylate H4 ( 26 ). KAT6A has a function in regulating H3K23ac ( 63 ) and H3K9ac at specific loci ( 64 – 67 ).…”

Section: Discussionmentioning

confidence: 99%

“…KAT6A has a function in regulating H3K23ac ( 63 ) and H3K9ac at specific loci ( 64 – 67 ). H3K14ac and H3K23ac are the two most abundant histone acetylation modifications ( 68 ), suggesting that the complexes generating the modifications are present throughout the genome ( 62 ). However, there is an enrichment of at least H3K14ac and KAT7 at transcription start sites ( 62 , 69 ).…”

Section: Discussionmentioning

confidence: 99%

“…H3K14ac and H3K23ac are the two most abundant histone acetylation modifications ( 68 ), suggesting that the complexes generating the modifications are present throughout the genome ( 62 ). However, there is an enrichment of at least H3K14ac and KAT7 at transcription start sites ( 62 , 69 ). Transcription start sites are also enriched for H3K4me3 ( 7 , 18 ), the modification bound by ING5 ( 3 , 8 ).…”

Section: Discussionmentioning

confidence: 99%

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The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver

et al. 2023

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ING5 is a component of KAT6A and KAT7 histone lysine acetylation protein complexes. ING5 contains a PHD domain that binds to histone H3 lysine 4 when it is trimethylated, and so functions as a ‘reader’ and adaptor protein. KAT6A and KAT7 function are critical for normal hematopoiesis. To examine the function of ING5 in hematopoiesis, we generated a null allele of Ing5. Mice lacking ING5 during development had decreased foetal liver cellularity, decreased numbers of hematopoietic stem cells and perturbed erythropoiesis compared to wild-type control mice. Ing5–/– pups had hypoplastic spleens. Competitive transplantation experiments using foetal liver hematopoietic cells showed that there was no defect in long-term repopulating capacity of stem cells lacking ING5, suggesting that the defects during the foetal stage were not cell intrinsic. Together, these results suggest that ING5 function is dispensable for normal hematopoiesis but may be required for timely foetal hematopoiesis in a cell-extrinsic manner.

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“…To assess the functional requirement for the active retention of active chromatin and local loss of repressive histone marks in transcriptional memory at GBP genes, we depleted the writers for these marks in the context of IFN priming and memory. First, we targeted the H3K14ac writer, KAT7 (also known as MYST2/HBO1) 19,20 as this mark is strongly maintained in the primed state, post-stimulation (Fig. 1C, D).…”

Section: The Writers For H3k14ac and H3k27me3 Are Functionally Requir...mentioning

confidence: 99%

Transcriptional memory is conferred by combined heritable maintenance and local removal of selective chromatin modifications

Mikulski,

Tehrani,

Kogan

et al. 2023

Preprint

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Interferon-γ (IFNγ) transiently activates genes involved in inflammation and innate immunity. A subset of targets maintain a mitotically heritable memory of prior IFNγ exposure resulting in hyperactivation upon reexposure. Here we discovered that the active chromatin marks H3K4me1, H3K14Ac and H4K16Ac are established during IFNγ priming and selectively maintained on a cluster of GBP genes for at least 7 days in dividing cells in the absence of transcription. The histone acetyltransferase KAT7 is required for the accelerated GBP reactivation upon reexposure to IFNγ. In naïve cells, we find the GBP cluster is maintained in low-level repressive chromatin marked by H3K27me3 limiting priming in a PRC2-dependent manner. Unexpectedly, IFNγ results in transient accumulation of this repressive mark but is then selectively depleted from primed GBP genes during the memory phase facilitating hyperactivation of primed cells. Furthermore, we identified a cis-regulatory element that makes transient, long-range contacts across the GBP cluster and acts as a repressor, primarily to curb the hyperactivation of previously IFNγ-primed cells. Combined our results identify the putative chromatin basis for long-term transcriptional memory of interferon signalling that may contribute to enhanced innate immunity.

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Stem cell plasticity, acetylation of H3K14, and de novo gene activation rely on KAT7

Cited by 6 publications

References 97 publications

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

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

The chromatin reader protein ING5 is required for normal hematopoietic cell numbers in the fetal liver

Transcriptional memory is conferred by combined heritable maintenance and local removal of selective chromatin modifications

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