Abstract
Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.
Highlights
Histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-amino groups of lysine residues
Class I HDACs are ubiquitously expressed nuclear proteins. These enzymes share a high level of sequence homology and common substrates, and HDAC2 can partially compensate for Histone Deacetylase 1 (HDAC1) loss, each of the enzymes has a unique role in cell function, as deletion of each member of the class I deacetylase leads to lethality
The total deacetylase enzymatic activity is greatly reduced in HDAC1 null ES cells, indicating that HDAC1 is a major deacetylase in ES cells [10]
Summary
Histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-amino groups of lysine residues. The reversible acetylation of histones and non-histone proteins by histone acetyltransferases (HATs) and HDACs play critical roles in transcriptional regulation in eukaryotic cells. Non-histone protein lysine acetylation plays a diverse role in the regulation of all aspects of cellular processes that may result in transcription activation or repression [3,4,5,6]. Class I HDACs are ubiquitously expressed nuclear proteins These enzymes share a high level of sequence homology and common substrates, and HDAC2 can partially compensate for HDAC1 loss, each of the enzymes has a unique role in cell function, as deletion of each member of the class I deacetylase leads to lethality (reviewed in [7]). It is extremely important to understand how HDAC affects normal hematopoiesis
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