Principles for the regulation of multiple developmental pathways by a versatile transcriptional factor, BLIMP1.
Principles for the regulation of multiple developmental pathways by a versatile transcriptional factor, BLIMP1.
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DOI：
10.1093/nar/gkx798
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发表时间：
2017-12-01
影响因子：
14.9
通讯作者：
Kurimoto K
中科院分区：
文献类型：
--
作者：
Mitani T;Yabuta Y;Ohta H;Nakamura T;Yamashiro C;Yamamoto T;Saitou M;Kurimoto K
单一转录因子（TF）调节多种发育途径，但其潜在机制仍不清楚。在这里，我们定量描述了 BLIMP1 在三种胚层衍生物（光感受器前体、胚胎肠上皮和浆母细胞）和生殖细胞谱系（原始生殖细胞）发育过程中的全基因组占用概况，BLIMP1 是多种发育过程的关键转录调节因子。我们鉴定了多个发育过程中共享的 BLIMP1 结合位点，这些位点被具有严格识别基序的 BLIMP1 高度占据，并且主要位于启动子附近。所有谱系共有的结合子集表现出新的、强识别序列，即 GGGAAA 重复序列。然而，矛盾的是，共享/共同的结合对相关基因表达只有轻微的影响。相比之下，BLIMP1以细胞类型特异性的方式占据了更远端的位点；尽管占用率较低且序列识别灵活，但这种结合有效地有助于抑制相关基因。 BLIMP1 结合位点中其他关键 TF 的识别基序对表达水平变化影响不大。这些发现表明，共享/共同位点可能作为在特定位点发挥作用的 BLIMP1 的潜在储存库，为统一理解 BLIMP1 以及可能的 TF 的基因组调控奠定了基础。
Single transcription factors (TFs) regulate multiple developmental pathways, but the underlying mechanisms remain unclear. Here, we quantitatively characterized the genome-wide occupancy profiles of BLIMP1, a key transcriptional regulator for diverse developmental processes, during the development of three germ-layer derivatives (photoreceptor precursors, embryonic intestinal epithelium and plasmablasts) and the germ cell lineage (primordial germ cells). We identified BLIMP1-binding sites shared among multiple developmental processes, and such sites were highly occupied by BLIMP1 with a stringent recognition motif and were located predominantly in promoter proximities. A subset of bindings common to all the lineages exhibited a new, strong recognition sequence, a GGGAAA repeat. Paradoxically, however, the shared/common bindings had only a slight impact on the associated gene expression. In contrast, BLIMP1 occupied more distal sites in a cell type-specific manner; despite lower occupancy and flexible sequence recognitions, such bindings contributed effectively to the repression of the associated genes. Recognition motifs of other key TFs in BLIMP1-binding sites had little impact on the expression-level changes. These findings suggest that the shared/common sites might serve as potential reservoirs of BLIMP1 that functions at the specific sites, providing the foundation for a unified understanding of the genome regulation by BLIMP1, and, possibly, TFs in general.
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影响因子：
64.5
作者：
Long, Hannah K.;Prescott, Sara L.;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
4.4
作者：
Kuo, TC;Calame, KL
通讯作者：
Calame, KL
影响因子：
14.9
作者：
Kazemian M;Pham H;Wolfe SA;Brodsky MH;Sinha S
通讯作者：
Sinha S
影响因子：
56.9
作者：
Lin, Y;Wong, KK;Calame, K
通讯作者：
Calame, K