Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.
Essential role of chromatin remodeling protein Bptf in early mouse embryos and embryonic stem cells.
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DOI：
10.1371/journal.pgen.1000241
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发表时间：
2008-10
期刊：
影响因子：
4.5
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Landry J;Sharov AA;Piao Y;Sharova LV;Xiao H;Southon E;Matta J;Tessarollo L;Zhang YE;Ko MS;Kuehn MR;Yamaguchi TP;Wu C
We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. While the chromatin of eukaryotes provides an efficient means to compact large amounts of DNA into a small nucleus, it renders the DNA relatively inaccessible. ATP-dependent chromatin remodeling complexes mobilize nucleosomes and provide a means to gain access to DNA in chromatin. While the biochemical functions of chromatin remodeling complexes is well-characterized, less is known of their biological functions. In this manuscript, we elucidate the biological functions of Bptf, a subunit of the NURF chromatin remodeling complex. Our studies show that Bptf is required for the establishment of the anterior–posterior axis of the mouse embryo during the earliest stages of development. To understand its functions in tissue differentiation, we generated and characterized Bptf-mutant ES cells. Mutant embryonic stem cells show significant defects in the differentiation of ectoderm, endoderm, and mesoderm. Genome-wide analysis of gene expression defects during differentiation has identified many Bptf-dependent pathways including key regulators of ectoderm, endoderm, and mesoderm differentiation. Moreover, we have identified critical functions for Bptf during the TGFβ/Smad-induced expression of visceral endoderm and mesoderm markers, an important signaling pathway in the early embryo. These results suggest that chromatin remodeling by Bptf regulates key signaling pathways in the early mouse embryo.
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DOI：
10.1073/pnas.95.9.5082
发表时间：
1998-04-28
影响因子：
11.1
作者：
Arman, E;Haffner-Krausz, R;Lonai, P
通讯作者：
Lonai, P
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
64.5
作者：
Bao, Yunhe;Shen, Xuetong
通讯作者：
Shen, Xuetong
影响因子：
64.8
作者：
Ding, JX;Yang, L;Shen, MM
通讯作者：
Shen, MM