Identification of the transcription factor MAZ as a regulator of erythropoiesis

Abstract

Erythropoiesis requires a combination of ubiquitous and tissue-specific transcription factors (TFs). Here, through DNA affinity purification followed by mass spectrometry, we have identified the widely expressed protein MAZ (Myc-associated zinc finger) as a TF that binds to the promoter of the erythroid-specific human α-globin gene. Genome-wide mapping in primary human erythroid cells revealed that MAZ also occupies active promoters as well as GATA1-bound enhancer elements of key erythroid genes. Consistent with an important role during erythropoiesis, knockdown of MAZ reduces α-globin expression in K562 cells and impairs differentiation in primary human erythroid cells. Genetic variants in the MAZ locus are associated with changes in clinically important human erythroid traits. Taken together, these findings reveal the zinc-finger TF MAZ to be a previously unrecognized regulator of the erythroid differentiation program.

The transcriptional and epigenetic reprogramming associated with chronic IL1β-mediated expansion and myeloid priming in TET2 deficient stem and progenitor cells

“…Notably, Tet2-KO LSKs relative to WT upon IL1β stimulation had the highest percentage of their probes hypermethylated for lymphoid enhancers, followed by myeloid, and erythroid enhancers. In contrast, the opposite pattern was observed in Tet2-KO CMPs relative to WT upon IL1β stimulation in which erythroid [34][35][36] . The latter two binding sites were in the top 10 for methylation increase at steady state.…”

“…To further validate this finding, we used published ChIP-seq data for 35 proteins including transcription factors (TFs) and epigenetic modifiers with roles in maintenance of HSC function, differentiation, or inflammation. The top 10 TF binding sites with the highest methylation increase in Tet2-KO relative to WT upon IL1β stimulation in CMPs included GATA1, TAL1, and MAZ which promote erythropoiesis (Fig 5c) [34][35][36] . The latter two binding sites were in the top 10 for methylation increase at steady state.…”

Roles of Myc‐associated zinc finger protein in malignant tumors

“…53 A recent study showed that MAZ was a transferrin that bound to the erythroid-specific human globin gene promoter and may regulate the erythroid differentiation program. 54 In addition to the above positive effects, MAZ was also identified as a growth inhibitor in mouse embryonic fibroblasts. 55 Xie et al 11 found that the hypoxia-inducible factor 2α (HIF2α) can interact with MAZ, and HIF2α activated the expression of CAV1 in a MAZ-dependent manner, promoted the destruction of intestinal tight junctions, and increased the permeability of the intestinal barrier, leading to hypoxiainduced intestinal inflammation happened (Table 1).…”

“…MAZ has also been identified as a transcriptional regulator of muscle‐specific genes in skeletal and cardiac myocytes, transactivating the muscle creatine kinase (MCK) promoter by binding to the MCK promoter element X (MPEX) site, whereas MCK is essential for maintaining the normal function of muscle cells 53 . A recent study showed that MAZ was a transferrin that bound to the erythroid‐specific human globin gene promoter and may regulate the erythroid differentiation program 54 …”

Epigenetic and Transcriptional Control of Erythropoiesis

“…( Jayapal et al, 2010 ). In addition, the transcriptional regulator MAZ (MYC-associated zinc finger) occupies the alpha globin promoter and regulates erythroid maturation ( Deen et al, 2021 ) and the transcription factor IKAROS contributes to gamma globin repression through recruitment of HDAC1 to the gamma globin promoter. ( Bottardi et al, 2009 ).It is also important to note that epigenetic modifiers can regulate the expression of transcription factors.…”