Identification of a novel putative mitochondrial protein FAM210B associated with erythroid differentiation

Abstract

The transcription factor GATA-1 plays an essential role in erythroid differentiation. To identify novel GATA-1 target genes, we analyzed a merged ChIP-seq and expression profiling dataset. We identified FAM210B as a putative novel GATA-1 target gene. Study results demonstrated that GATA-1 directly regulates FAM210B expression, presumably by binding to an intronic enhancer region. Both human and murine FAM210B are abundantly expressed in the later stages of erythroblast development. Moreover, the deduced amino acid sequence predicted that FAM210B is a membrane protein, and Western blot analysis demonstrated its mitochondrial localization. Loss-of-function analysis in erythroid cells suggested that FAM210B may be involved in erythroid differentiation. The identification and characterization of FAM210B provides new insights in the study of erythropoiesis and hereditary anemias.

FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity

“…In addition, FAM210B regulates FECH enzyme activity. Our results are consistent with and extend the findings of a recent study identifying Fam210b as a GATA1 transcriptional target that is required for erythroid differentiation (29). Mitochondrial mass, membrane potential, and porphyrin levels are normal in Fam210b Ϫ/Ϫ cells, precluding a role for FAM210B in housekeeping mitochondrial homeostasis or tetrapyrrole synthesis, respectively.…”

“…Fam210b is transcriptionally activated by GATA-1 (29,56), consistent with its expression in erythropoietic tissues. Iron chelation by DFO or iron supplementation by iron citrate did not cause changes in its steady-state protein expression, indicating that FAM210B is not regulated by cellular iron status (Fig.…”

“…One candidate gene, Fam210b (C20orf120), encoded a protein containing an N-terminal mitochondrial-targeting sequence. Fam210b was previously described to be a target of the erythroid transcription factor, GATA1, which encoded a mitochondrial-localized protein (29) that regulates mitochondrial metabolism in nonerythroid cells (30). In this study, we decided to interrogate the role of Fam210b in erythroid physiology.…”

Loss of the novel mitochondrial protein FAM210B promotes metastasis via PDK4-dependent metabolic reprogramming

“…A recent new study identified it as a putative mitochondrial protein using transiently transfected His/Myc-tagged FAM210B and to be involved in erythroid differentiation. 16 Our observation revealed that different cell lines express FAM210B and FAM210B was an outer membrane protein of the mitochondria with an N-terminal 47 aa MTS (Figure 4). These findings suggest that the novel mitochondrial protein FAM210B may connect mitochondrial function to cancer progression.…”

Generation and Molecular Characterization of Human Ring Sideroblasts: a Key Role of Ferrous Iron in Terminal Erythroid Differentiation and Ring Sideroblast Formation

“…We next performed fluorescence-activated cell sorting (FACS) analysis to test whether coculture with OP9 cells altered the erythroid differentiation stage. During erythroid differentiation, TfR1 expression precedes GPA (also denoted CD235a) expression and subsequently decreases in the terminal stages (28). The TfR1 Ϫ GPA ϩ mature erythroid population significantly increased following the addition of SFC after coculturing in wild-type HiDEP cells (Fig.…”