Emerging roles of bromodomain protein 4 in regulation of stem cell identity,STEM CELLS

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Emerging roles of bromodomain protein 4 in regulation of stem cell identity
STEM CELLS ( IF 4.0 ) Pub Date : 2021-09-14 , DOI: 10.1002/stem.3454
Anusree Dey _{1,

2} , Sheetal Uppal _{1,

2} , Jayeeta Giri ₃ , Hari Sharan Misra _{1,

2}

Affiliation

Understanding the mechanism of fate decision and lineage commitment is the key step for developing novel stem cell applications in therapeutics. This process is coordinately regulated through systematic epigenetic reprogramming and concomitant changes in the transcriptional landscape of the stem cells. One of the bromo- and extra-terminal domain (BET) family member proteins, bromodomain protein 4 (BRD4), performs the role of epigenetic reader and modulates gene expression by recruiting other transcription factors and directly regulating RNA polymerase II elongation. Controlled gene regulation is the critical step in maintenance of stem cell potency and dysregulation may lead to tumor formation. As a key transcriptional factor and epigenetic regulator, BRD4 contributes to stem cell maintenance in several ways. Being a druggable target, BRD4 is an attractive candidate for exploiting its potential in stem cell therapeutics. Therefore, it is crucial to elucidate how BRD4, through its interplay with pluripotency transcriptional regulators, control lineage commitment in stem cells. Here, we systemically review the role of BRD4 in complex gene regulatory network during three specific states of stem cell transitions: cell differentiation, cell reprogramming and transdifferentiation. A thorough understanding of BRD4 mediated epigenetic regulation in the maintenance of stem cell potency will be helpful to strategically control stem cell fates in regenerative medicine.

中文翻译：

溴结构域蛋白 4 在干细胞特性调节中的新作用

了解命运决定和谱系承诺的机制是开发新型干细胞在治疗中应用的关键步骤。这个过程通过系统的表观遗传重编程和干细胞转录景观的伴随变化来协调调节。溴结构域和外末端结构域 (BET) 家族成员蛋白之一，溴结构域蛋白 4 (BRD4)，发挥表观遗传阅读器的作用，并通过招募其他转录因子和直接调节 RNA 聚合酶 II 延伸来调节基因表达。受控基因调控是维持干细胞效力的关键步骤，失调可能导致肿瘤形成。作为关键的转录因子和表观遗传调节因子，BRD4 以多种方式促进干细胞维持。作为一个可药化的目标，BRD4 是利用其在干细胞治疗中的潜力的有吸引力的候选者。因此，阐明 BRD4 如何通过其与多能性转录调节因子的相互作用来控制干细胞中的谱系定型至关重要。在这里，我们系统地回顾了 BRD4 在干细胞转变的三个特定状态期间在复杂基因调控网络中的作用：细胞分化、细胞重编程和转分化。全面了解 BRD4 介导的表观遗传调控在维持干细胞效力中的作用将有助于战略性地控制再生医学中的干细胞命运。控制干细胞中的谱系定型。在这里，我们系统地回顾了 BRD4 在干细胞转变的三个特定状态期间在复杂基因调控网络中的作用：细胞分化、细胞重编程和转分化。全面了解 BRD4 介导的表观遗传调控在维持干细胞效力中的作用将有助于战略性地控制再生医学中的干细胞命运。控制干细胞中的谱系定型。在这里，我们系统地回顾了 BRD4 在干细胞转变的三个特定状态期间在复杂基因调控网络中的作用：细胞分化、细胞重编程和转分化。全面了解 BRD4 介导的表观遗传调控在维持干细胞效力中的作用将有助于战略性地控制再生医学中的干细胞命运。

更新日期：2021-09-14

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