Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891557180> ?p ?o ?g. }
Showing items 1 to 63 of
63
with 100 items per page.
- W2891557180 abstract "MOZ (also known as KAT6A and MYST3) is a histone acetyltransferase that is implicated in the development of hematopoietic, heart and craniofacial tissues. Reciprocal translocations generating MOZ fusion proteins are associated with acute myeloid leukaemia (AML), a heterogeneous hematopoietic stem cell disorder where the myeloid cells do not enter into differentiation process, resulting in accumulation of blast cells and absence of a fully functional granulocyte lineage. Also, mutations that truncate the C-terminus of MOZ are associated with global developmental delay. Mechanistically, it is known that MOZ acts as a cofactor for certain transcription factors, particularly those with haematopoietic or neuronal specificity, such as acute myeloid leukaemia/Runt-related transcription factor 1 (AML1/RUNX1) and PU.1. However, at the outset of this project, it was relatively unknown which genes that are regulated by MOZ in leukaemia. Thus, this work investigates MOZ target genes in a leukemic cell line to fully understand its importance in cell function and disease conditions.Firstly, we performed siRNA silencing in K562 cell line, coupled with transcription profiling by RNA sequencing. We identified 406 deregulated genes under MOZ knockdown, of which 76 were downregulated. Many of the MOZ-target genes identified are implicated in haematopoietic development and cell proliferation. Secondly, we generated MOZ/KAT6A knockout K562 cells using CRISPR CAS9n nickase technology. It allowed further analysis of the function of MOZ in leukaemia. Our results confirmed the role of MOZ in maintaining levels of H3K14ac and H3K9ac and an apparent inverse relationship with the levels of H3K14 crotonylation. Furthermore, the results indicated that MOZ is important for leukemic cell proliferation and the gene dosage influences on the cell proliferation rate. Finally, we found that genes requiring MOZ for their expression are sensitive to a novel class of bromodomain inhibitors called iBETs. Furthermore, we found evidence for the existence of MOZ in complex with BRD4 protein. This provides a hitherto unknown link between MOZ, MLL and BRD2-4 complexes and insight into how these epigenetic regulators cooperate to control gene expression." @default.
- W2891557180 created "2018-09-27" @default.
- W2891557180 creator A5061985503 @default.
- W2891557180 date "2018-07-19" @default.
- W2891557180 modified "2023-09-23" @default.
- W2891557180 title "Function of MYST3/MOZ, a histone acetyltransferase and chromatin regulator implicated in haematopoietic stem cell development and leukaemia" @default.
- W2891557180 hasPublicationYear "2018" @default.
- W2891557180 type Work @default.
- W2891557180 sameAs 2891557180 @default.
- W2891557180 citedByCount "0" @default.
- W2891557180 crossrefType "dissertation" @default.
- W2891557180 hasAuthorship W2891557180A5061985503 @default.
- W2891557180 hasConcept C104317684 @default.
- W2891557180 hasConcept C109159458 @default.
- W2891557180 hasConcept C119056186 @default.
- W2891557180 hasConcept C2778001298 @default.
- W2891557180 hasConcept C2778193527 @default.
- W2891557180 hasConcept C28328180 @default.
- W2891557180 hasConcept C502942594 @default.
- W2891557180 hasConcept C54355233 @default.
- W2891557180 hasConcept C83640560 @default.
- W2891557180 hasConcept C86339819 @default.
- W2891557180 hasConcept C86803240 @default.
- W2891557180 hasConcept C95444343 @default.
- W2891557180 hasConceptScore W2891557180C104317684 @default.
- W2891557180 hasConceptScore W2891557180C109159458 @default.
- W2891557180 hasConceptScore W2891557180C119056186 @default.
- W2891557180 hasConceptScore W2891557180C2778001298 @default.
- W2891557180 hasConceptScore W2891557180C2778193527 @default.
- W2891557180 hasConceptScore W2891557180C28328180 @default.
- W2891557180 hasConceptScore W2891557180C502942594 @default.
- W2891557180 hasConceptScore W2891557180C54355233 @default.
- W2891557180 hasConceptScore W2891557180C83640560 @default.
- W2891557180 hasConceptScore W2891557180C86339819 @default.
- W2891557180 hasConceptScore W2891557180C86803240 @default.
- W2891557180 hasConceptScore W2891557180C95444343 @default.
- W2891557180 hasLocation W28915571801 @default.
- W2891557180 hasOpenAccess W2891557180 @default.
- W2891557180 hasPrimaryLocation W28915571801 @default.
- W2891557180 hasRelatedWork W1122578023 @default.
- W2891557180 hasRelatedWork W1491133549 @default.
- W2891557180 hasRelatedWork W1966951090 @default.
- W2891557180 hasRelatedWork W1995752013 @default.
- W2891557180 hasRelatedWork W2028600062 @default.
- W2891557180 hasRelatedWork W2131619970 @default.
- W2891557180 hasRelatedWork W2146621640 @default.
- W2891557180 hasRelatedWork W2152487267 @default.
- W2891557180 hasRelatedWork W2154371397 @default.
- W2891557180 hasRelatedWork W2551477821 @default.
- W2891557180 hasRelatedWork W2553249337 @default.
- W2891557180 hasRelatedWork W2567140571 @default.
- W2891557180 hasRelatedWork W2617840184 @default.
- W2891557180 hasRelatedWork W2896433555 @default.
- W2891557180 hasRelatedWork W2905733679 @default.
- W2891557180 hasRelatedWork W2979817950 @default.
- W2891557180 hasRelatedWork W2982130801 @default.
- W2891557180 hasRelatedWork W3016898368 @default.
- W2891557180 hasRelatedWork W3084033843 @default.
- W2891557180 hasRelatedWork W3087415019 @default.
- W2891557180 isParatext "false" @default.
- W2891557180 isRetracted "false" @default.
- W2891557180 magId "2891557180" @default.
- W2891557180 workType "dissertation" @default.