The Role Of Histone Deacetylases (HDACs) During Hematopoiesis

Histone deacetylases are capable of modifying their target proteins, removingacetyl residue from a lysine of their substrate. Meanwhile, histone acetyl-transferasescan add an acetyl residue to their substrates to keep the protein acetylation levelbalance in vivo, regulating cell proliferation and differentiation. GATA-1, as atranscription factor, is capable of recognizing WGATAR region of DNA, and it isquite critical for blood cell differentiation since paper has been reported that GATA-1knock out mice die between E10.5and E11.5due to anemia. GATA1can recruitdifferent proteins and complexes to regulate the activation or inhibition of its targetgenes. This activation or inhibition depends on the function of GATA1recruitedproteins or complexes. FOG1is a direct target of GATA1, which contains zincfingers domain that can bind to GATA1directly. FOG1knock out mice die due to thesimilar reason as GATA1knock out mice, indicating FOG1and GATA1haveoverlap function. HDAC1and HDAC2containing complex NuRD can be associatedwith GATA-1through FOG1. But it remains unclear why NuRD complex, usuallyconsidered as co-repressor, exist at both GATA1activated and repressed genes’promoter. In our experiment, it has been proved that HDAC1and GATA-1caninteract with each other directly, and the acetylation level of HDAC1which isassociated with GATA-1plays an important role in regulating GATA-1target genesexpression during erythropoiesis. Acetylation of HDAC1can convert HDAC1containing co-repressor complex into co-activator complex. This has been proved onseveral erythroid models in our experiment data. HDAC6acts as a deacetylase,existing in both nuclei and cytoplasm. It also functions during terminalerythropoiesis, especial the enucleation stage. HDAC6knock down MEL showssignificant enucleation defect, and causes lower mature erythocytes number,indicating its function during enucleation.