Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci.
Differential coregulator requirements for function of the hematopoietic transcription factor GATA-1 at endogenous loci.
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DOI：
10.1093/nar/gkp1159
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发表时间：
2010-04
影响因子：
14.9
通讯作者：
Bresnick EH
中科院分区：
文献类型：
--
作者：
Pope NJ;Bresnick EH
造血的关键调节因子加塔-1将不同的辅助调节因子募集到染色质，其介导转录激活和抑制。这些辅助调节因子包括细胞类型特异性多锌指蛋白Friend of加塔-1（FOG-1）、组蛋白乙酰转移酶CREB结合蛋白（CBP）和介体复合物Med 1的关键组分。虽然FOG-1是一个既定的加塔-1共调节，加塔-1和其他共调节之间的相互作用的重要性知之甚少。此外，加塔-1是否在所有基因座利用多个辅调节子，或者某些辅调节子是否专用于特定基因座尚不清楚。我们比较了加塔-1在激活和抑制的靶基因上募集和利用FOG-1和Med 1的能力。与FOG-1相似，加塔-1将Med 1募集到激活的基因，并且FOG-1和Med 1募集的动力学相似。加塔-1在Fog 1 −/−细胞中募集Med 1，表明加塔-1介导的Med 1募集是不依赖于FOG-1的。与FOG-1相反，加塔-1在转录抑制期间驱逐Med 1。敲低FOG-1对加塔-1介导的激活和抑制具有灾难性影响，而敲低Med 1仅在选定位点适度损害加塔-1活性。这些结果说明了加塔-1介导的FOG-1和Med 1向染色质的募集之间的相似性和差异，根本差异是对FOG-1的数量需求更大。
The critical regulator of hematopoiesis GATA-1 recruits diverse coregulators to chromatin, which mediate transcriptional activation and repression. These coregulators include the cell-type-specific multi-zinc finger protein Friend of GATA-1 (FOG-1), the histone acetyltransferase CREB binding protein (CBP), and the key component of the Mediator complex Med1. While FOG-1 is an established GATA-1 coregulator, the importance of interactions between GATA-1 and other coregulators is poorly understood. Furthermore, whether GATA-1 utilizes multiple coregulators at all loci, or if certain coregulators are dedicated to specific loci is unknown. We compared the capacity of GATA-1 to recruit and utilize FOG-1 and Med1 at activated and repressed target genes. Similar to FOG-1, GATA-1 recruited Med1 to activated genes, and the kinetics of FOG-1 and Med1 recruitment were similar. GATA-1 recruited Med1 in Fog1−/− cells, indicating that GATA-1-mediated Med1 recruitment is FOG-1-independent. In contrast to FOG-1, GATA-1 evicted Med1 during transcriptional repression. Whereas knocking-down FOG-1 had catastrophic effects on GATA-1-mediated activation and repression, knocking-down Med1 modestly impaired GATA-1 activity only at select loci. These results illustrate both similarities and differences between GATA-1-mediated recruitment of FOG-1 and Med1 to chromatin, with a fundamental difference being the quantitatively greater requirement for FOG-1.
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影响因子：
16
作者：
Fujiwara T;O'Geen H;Keles S;Blahnik K;Linnemann AK;Kang YA;Choi K;Farnham PJ;Bresnick EH
通讯作者：
Bresnick EH
DOI：
10.1073/pnas.0604041103
发表时间：
2006-10-24
影响因子：
11.1
作者：
Johnson, Kirby D.;Kim, Shin-Il;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
影响因子：
20.3
作者：
Johnson, Kirby D.;Boyer, Meghan E.;Bresnick, Emery H.
通讯作者：
Bresnick, Emery H.
影响因子：
16
作者：
Crispino, JD;Lodish, MB;Orkin, SH
通讯作者：
Orkin, SH
DOI：
10.1073/pnas.0511150103
发表时间：
2006-02-28
影响因子：
11.1
作者：
Bourquin, JP;Subramanian, A;Orkin, SH
通讯作者：
Orkin, SH