Unknown,Transcriptomics,Genomics,Proteomics

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TRIM28 is essential for erythroblast differentiation in the mouse

ABSTRACT: We discovered that Trim28 genetic loss in the adult mouse leads to defective immature erythropoiesis in the bone marrow and consequently to anemia.We further found that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of TRIM28 we observed increased apoptosis as well as diminished expression of multiple erythroid transcription factors and heme biosynthetic enzymes in immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous development of immature erythroblasts in the bone marrow. To induce Cre recombinase from the Mx1Cre transgene, poly(I:C) was injected 5 times every other day. Mice were analyzed two weeks after completion of poly(I:C) administration. TRIM28 mutant mice generate two distinct types of immature erythroid cells; KOa, with 5-8% of the Trim28 gene remaining undeleted (still bearing 26% of residual mRNA), and KOb, with 1-4% of the gene remaining undeleted (and with 18% of mRNA remaining).

ORGANISM(S): Mus musculus

SUBMITTER: Tomonori Hosoya

PROVIDER: E-GEOD-49843 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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TRIM28 is essential for erythroblast differentiation in the mouse.

Hosoya Tomonori T Clifford Mary M Losson Régine R Tanabe Osamu O Engel James Douglas JD

Blood 20131003 23

In previous mass spectrometry and coimmune precipitation studies, we identified tripartite motif-containing 28 (TRIM28; also known as transcriptional intermediary factor1β and Krüppel-associated box-associated protein-1) as a cofactor that specifically copurified with an NR2C1/NR2C2 (TR2/TR4) orphan nuclear receptor heterodimer that previous studies had implicated as an embryonic/fetal β-type globin gene repressor. TRIM28 has been characterized as a transcriptional corepressor that can associate ...[more]

PMID: 24092935

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Project description:Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation. PBMC-derived erythroblasts grown in vitro were harvested at the CFU-E, Pro-E, Int-E and Late-E stages and FACS sorted based on expression of cell surface markers. RNA was extracted from those populations which met rigorous specifications of time cultured in the presence of erythropoietin, morphology and CD36, CD71 and CD235a expression. For each stage, 3 chips were hybridised, each representing a pool of 4 different samples. In addition to these 12 chips, one chip representing a pool of RNA extracted from unsorted cells at each stages was also hybridised.

Dataset Information

TRIM28 is essential for erythroblast differentiation in the mouse

Publications

TRIM28 is essential for erythroblast differentiation in the mouse.

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