Cargando…

Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis

Homeostasis in the blood system is maintained by the balance between self‐renewing stem cells and nonstem cells. To promote self‐renewal, transcriptional regulators maintain epigenetic information during multiple rounds of cell division. Mutations in such transcriptional regulators cause aberrant se...

Descripción completa

Detalles Bibliográficos
Autor principal: Yokoyama, Akihiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078767/
https://www.ncbi.nlm.nih.gov/pubmed/34482632
http://dx.doi.org/10.1111/febs.16180
_version_ 1785020593058349056
author Yokoyama, Akihiko
author_facet Yokoyama, Akihiko
author_sort Yokoyama, Akihiko
collection PubMed
description Homeostasis in the blood system is maintained by the balance between self‐renewing stem cells and nonstem cells. To promote self‐renewal, transcriptional regulators maintain epigenetic information during multiple rounds of cell division. Mutations in such transcriptional regulators cause aberrant self‐renewal, leading to leukemia. MOZ, a histone acetyltransferase, and MLL, a histone methyltransferase, are transcriptional regulators that promote the self‐renewal of hematopoietic stem cells. Gene rearrangements of MOZ and MLL generate chimeric genes encoding fusion proteins that function as constitutively active forms. These MOZ and MLL fusion proteins constitutively activate transcription of their target genes and cause aberrant self‐renewal in committed hematopoietic progenitors, which normally do not self‐renew. Recent progress in the field suggests that MOZ and MLL are part of a transcriptional activation system that activates the transcription of genes with nonmethylated CpG‐rich promoters. The nonmethylated state of CpGs is normally maintained during cell divisions from the mother cell to the daughter cells. Thus, the MOZ/MLL‐mediated transcriptional activation system replicates the expression profile of mother cells in daughter cells by activating the transcription of genes previously transcribed in the mother cell. This review summarizes the functions of the components of the MOZ/MLL‐mediated transcriptional activation system and their roles in the promotion of self‐renewal.
format Online
Article
Text
id pubmed-10078767
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-100787672023-04-07 Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis Yokoyama, Akihiko FEBS J Review Articles Homeostasis in the blood system is maintained by the balance between self‐renewing stem cells and nonstem cells. To promote self‐renewal, transcriptional regulators maintain epigenetic information during multiple rounds of cell division. Mutations in such transcriptional regulators cause aberrant self‐renewal, leading to leukemia. MOZ, a histone acetyltransferase, and MLL, a histone methyltransferase, are transcriptional regulators that promote the self‐renewal of hematopoietic stem cells. Gene rearrangements of MOZ and MLL generate chimeric genes encoding fusion proteins that function as constitutively active forms. These MOZ and MLL fusion proteins constitutively activate transcription of their target genes and cause aberrant self‐renewal in committed hematopoietic progenitors, which normally do not self‐renew. Recent progress in the field suggests that MOZ and MLL are part of a transcriptional activation system that activates the transcription of genes with nonmethylated CpG‐rich promoters. The nonmethylated state of CpGs is normally maintained during cell divisions from the mother cell to the daughter cells. Thus, the MOZ/MLL‐mediated transcriptional activation system replicates the expression profile of mother cells in daughter cells by activating the transcription of genes previously transcribed in the mother cell. This review summarizes the functions of the components of the MOZ/MLL‐mediated transcriptional activation system and their roles in the promotion of self‐renewal. John Wiley and Sons Inc. 2021-09-16 2022-12 /pmc/articles/PMC10078767/ /pubmed/34482632 http://dx.doi.org/10.1111/febs.16180 Text en © 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Review Articles
Yokoyama, Akihiko
Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title_full Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title_fullStr Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title_full_unstemmed Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title_short Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
title_sort role of the moz/mll‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078767/
https://www.ncbi.nlm.nih.gov/pubmed/34482632
http://dx.doi.org/10.1111/febs.16180
work_keys_str_mv AT yokoyamaakihiko roleofthemozmllmediatedtranscriptionalactivationsystemforselfrenewalinnormalhematopoiesisandleukemogenesis