Thyroid hormone dependent transcriptional programming by TRβ requires SWI/SNF chromatin remodelers.

Thyroid hormone dependent transcriptional programming by TRβ requires SWI/SNF chromatin remodelers.
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DOI:
10.1093/nar/gkab1287
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发表时间:
2022-02-22
影响因子:
14.9
通讯作者:
Carr FE
Carr FE
中科院分区:
生物学2区
文献类型:
--
作者:
Gillis NE;Boyd JR;Tomczak JA;Frietze S;Carr FE

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甲状腺激素(3,5,3′ - 三碘 - L - 甲状腺原氨酸,T3)响应的转录调控是一个动态的且具有细胞类型特异性的过程,它在所有组织中维持细胞内稳态和特性。然而,我们在分子水平上对甲状腺激素受体(TR)作用机制的理解正在不断完善。我们采用一种综合基因组学方法来描绘和表征TRβ的顺反组,绘制染色质可及性的变化图谱,并获取正常人甲状腺细胞中响应T3的转录组变化。响应T3时,TRβ在基因组上的结合位点有显著变化,这与染色质可及性的差异以及SWI/SNF染色质重塑复合物的差异招募相关。我们进一步证明了BAF和PBAF SWI/SNF复合物选择性地招募到TRβ结合位点,揭示了在调节染色质可及性和基因表达方面新的差异性功能。我们的研究结果强调了TRβ与染色质相互作用以及辅调节因子活性协调的三种不同模式。
Transcriptional regulation in response to thyroid hormone (3,5,3′-triiodo-l-thyronine, T3) is a dynamic and cell-type specific process that maintains cellular homeostasis and identity in all tissues. However, our understanding of the mechanisms of thyroid hormone receptor (TR) actions at the molecular level are actively being refined. We used an integrated genomics approach to profile and characterize the cistrome of TRβ, map changes in chromatin accessibility, and capture the transcriptomic changes in response to T3 in normal human thyroid cells. There are significant shifts in TRβ genomic occupancy in response to T3, which are associated with differential chromatin accessibility, and differential recruitment of SWI/SNF chromatin remodelers. We further demonstrate selective recruitment of BAF and PBAF SWI/SNF complexes to TRβ binding sites, revealing novel differential functions in regulating chromatin accessibility and gene expression. Our findings highlight three distinct modes of TRβ interaction with chromatin and coordination of coregulator activity.
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