The hematopoietic regulator TAL1 is required for chromatin looping between the β-globin LCR and human γ-globin genes to activate transcription.
The hematopoietic regulator TAL1 is required for chromatin looping between the β-globin LCR and human γ-globin genes to activate transcription.
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造血调节剂TAL1是染色质在β-珠蛋白LCR和人γ-球蛋白基因之间循环以激活转录所必需的。
DOI：
10.1093/nar/gku072
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Kim A
中科院分区：
文献类型：
--
作者：
Yun WJ;Kim YW;Kang Y;Lee J;Dean A;Kim A
TAL 1是一种关键的造血转录因子，作为与加塔-1、LMO 2和Ldb 1的复合物的一部分，与大量红细胞基因的调控区结合。该复合物介导β-珠蛋白基因座控制区（LCR）和活性珠蛋白基因之间的长程相互作用，尽管TAL 1是两个DNA结合复合物成员之一，但其作用尚不清楚。为了探索TAL 1在人γ-珠蛋白基因转录激活中的作用，我们使用慢病毒短发夹RNA降低了红系K562细胞中TAL 1的表达，损害了其在β-珠蛋白基因座中的关联。在TAL 1敲减细胞中，γ-珠蛋白转录降低至35%，Gγ-珠蛋白基因与LCR的染色质环被破坏，基因座中复合体成员Ldb 1和LMO 2的占据率降低。然而，加塔-1结合，DNA酶I超敏位点的形成和几个组蛋白修饰在很大程度上保持在整个β-珠蛋白基因座。此外，TAL 1的过表达增加了γ-珠蛋白的转录，并增加了Gγ-珠蛋白基因与LCR之间的相互作用频率。这些结果表明，TAL 1在γ-珠蛋白基因和LCR之间的染色质环形成中起关键作用，这是γ-珠蛋白基因转录的关键步骤。
TAL1 is a key hematopoietic transcription factor that binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. The complex mediates long-range interaction between the β-globin locus control region (LCR) and active globin genes, and although TAL1 is one of the two DNA-binding complex members, its role is unclear. To explore the role of TAL1 in transcription activation of the human γ-globin genes, we reduced the expression of TAL1 in erythroid K562 cells using lentiviral short hairpin RNA, compromising its association in the β-globin locus. In the TAL1 knockdown cells, the γ-globin transcription was reduced to 35% and chromatin looping of the Gγ-globin gene with the LCR was disrupted with decreased occupancy of the complex member Ldb1 and LMO2 in the locus. However, GATA-1 binding, DNase I hypersensitive site formation and several histone modifications were largely maintained across the β-globin locus. In addition, overexpression of TAL1 increased the γ-globin transcription and increased interaction frequency between the Gγ-globin gene and LCR. These results indicate that TAL1 plays a critical role in chromatin loop formation between the γ-globin genes and LCR, which is a critical step for the transcription of the γ-globin genes.
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DOI：
10.1016/j.mrfmmm.2008.07.014
发表时间：
2008-12-01
影响因子：
2.3
作者：
Kiefer, Christine M.;Hou, Chunhui;Little, Jane A.;Dean, Ann
通讯作者：
Dean, Ann
影响因子：
4.8
作者：
Lecuyer, Eric;Lariviere, Simon;Hoang, Trang
通讯作者：
Hoang, Trang
影响因子：
20.3
作者：
Kiefer, Christine M.;Lee, Jongjoo;Dean, Ann
通讯作者：
Dean, Ann
影响因子：
14.9
作者：
Cho Y;Song SH;Lee JJ;Choi N;Kim CG;Dean A;Kim A
通讯作者：
Kim A
影响因子：
4.8
作者：
Kooren, Jurgen;Palstra, Robert-Jan;de Laat, Wouter
通讯作者：
de Laat, Wouter