MTB, the murine homolog of condensin II subunit CAP-G2, represses transcription and promotes erythroid cell differentiation

Abstract

Chromosome condensation is essential for proper segregation of duplicated sister chromatids in mitosis. Mammalian erythroid maturation is also associated with gradual nuclear condensation. However, few proteins that are directly involved in chromosome condensation during erythropoiesis have been identified. In this report, we show that MTB (more than blood), which was initially isolated in a yeast two-hybrid screen for proteins that interact with the basic helix-loop-helix (bHLH) protein stem cell leukemia (SCL), and later identified as the murine homolog of the condensin II subunit CAP-G2, participates in erythroid cell development. MTB interacts with SCL and another hematopoietic bHLH protein, E12, and is recruited to the nucleus by SCL and E12. In addition, MTB can repress SCL/E12-mediated transcriptional activation. Consistent with the model that MTB may function together with SCL/E12 heterodimer during erythroid cell development, MTB is highly expressed in the erythroid lineage and is upregulated upon erythroid differentiation. Moreover, overexpression of MTB promotes the terminal differentiation of the murine erythroleukemia erythroid cell line. Together, these findings demonstrate that the condensin II subunit MTB/mCAP-G2 plays a novel function during erythropoiesis and suggest that key hematopoietic transcription factors such as SCL and E12 may regulate the terminal differentiation of hematopoietic cells through the interaction with condensin complexes.

Condensins: universal organizers of chromosomes with diverse functions

“…These results suggest that condensin II regulates a developmentally programmed cycle of chromatin condensation and decondensation that has a great impact on T-cell differentiation. Intriguingly, similar if not identical chromatin condensation is observed during erythroid cell differentiation, and the condensin II subunit CAP-G2 is implicated in this process and accompanying transcriptional repression (Xu et al 2006).…”

“…The characteristic behaviors of the two condensin complexes are most likely to be central to our understanding of their action and regulation. At the level of ontogeny, knocking out the gene encoding the CAP-G2 subunit in mice has been shown to cause embryonic lethality (Smith et al 2004;Xu et al 2006). Whereas knockout mice for the other subunits have not yet been described, all of them are anticipated to be essential for embryogenesis.…”

RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3

“…dCAP-G, (a member of both Condensin I and II) has been shown to effect position effect variegation (PEV), suggesting that it may have a role in maintenance of heterochromatin (Dej et al 2004;Cobbe et al 2006). An interaction between murine CAP-G2 (MTB) and the SCL and E12 transcription factors allows MTB to repress transcription during erythoid cell development (Xu et al 2006). Recently, a kleisin ␤ mutation in mice was shown to be responsible for defects in T-lymphocyte differentiation (Gosling et al 2007).…”

Drosophila Condensin II subunit Chromosome-associated Protein-D3 regulates cell fate determination through non-cell-autonomous signaling

“…The CAP-D3 subunit of Condensin II regulates the transcription of many genes during the larval and adult stages in the fly, including genes involved in cell fate determination (Longworth et al, 2012). Although Condensin II components have been shown to be necessary for the differentiation of mouse ESCs (Dowen et al, 2013), development of T cells (Rawlings et al, 2011) and differentiation of erythroid progenitors (Xu et al, 2006), a role for these subunits in promoting a choice between two cell fates in vivo has not been reported.…”