Premium
Altering chromatin methylation patterns and the transcriptional network involved in regulation of hematopoietic stem cell fate
Author(s) -
Shokouhian Mohammad,
Bagheri Marziye,
Poopak Behzad,
Chegeni Rouzbeh,
Davari Nader,
Saki Najmaldin
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29642
Subject(s) - biology , epigenetics , dna methylation , epigenetic regulation of neurogenesis , microbiology and biotechnology , epigenetics of physical exercise , chromatin , transcription factor , enhancer , histone , regulation of gene expression , genetics , histone methylation , chromatin remodeling , gene expression , gene
Hematopoietic stem cells (HSCs) are quiescent cells with self‐renewal capacity and potential multilineage development. Various molecular regulatory mechanisms such as epigenetic modifications and transcription factor (TF) networks play crucial roles in establishing a balance between self‐renewal and differentiation of HSCs. Histone/DNA methylations are important epigenetic modifications involved in transcriptional regulation of specific lineage HSCs via controlling chromatin structure and accessibility of DNA. Also, TFs contribute to either facilitation or inhibition of gene expression through binding to enhancer or promoter regions of DNA. As a result, epigenetic factors and TFs regulate the activation or repression of HSCs genes, playing a central role in normal hematopoiesis. Given the importance of histone/DNA methylation and TFs in gene expression regulation, their aberrations, including changes in HSCs‐related methylation of histone/DNA and TFs (e.g., CCAAT‐enhancer‐binding protein α, phosphatase and tensin homolog deleted on the chromosome 10, Runt‐related transcription factor 1, signal transducers and activators of transcription, and RAS family proteins) could disrupt HSCs fate. Herewith, we summarize how dysregulations in the expression of genes related to self‐renewal, proliferation, and differentiation of HSCs caused by changes in epigenetic modifications and transcriptional networks lead to clonal expansion and leukemic transformation.