The Drosophila HP1 family is associated with active gene expression across chromatin contexts
The Drosophila HP1 family is associated with active gene expression across chromatin contexts
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DOI：
10.1093/genetics/iyab108
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发表时间：
2021-07-14
期刊：
影响因子：
3.3
通讯作者：
Riddle，Nicole C.
中科院分区：
文献类型：
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作者：
Schoelz，John M.;Feng，Justina X.;Riddle，Nicole C.
果蝇异染色质蛋白1a（Heterochromatin Protein 1a，HP 1a）是异染色质形成所必需的蛋白质，参与转录沉默。然而，某些位点需要HP 1a转录。一个模型假定，HP 1a作为一个转录沉默在常染色质内，而作为一个激活异染色质。然而，已观察到HP 1a作为一组常染色质基因的激活剂。因此，尚不清楚染色质背景是否或如何告知HP 1蛋白的功能。为了了解HP 1蛋白在转录中的作用，我们研究了HP 1a以及另外两个果蝇HP 1家族成员HP 1B和HP 1C的全基因组结合谱，以确定这些蛋白的协调结合是否与特定的转录结果相关。我们发现，HP 1蛋白共享许多内源性结合靶点。这些基因以活跃的组蛋白修饰为标志，在异染色质和常染色质中的表达水平高于非靶基因。此外，与非靶基因相比，HP 1结合靶基因显示RNA聚合酶暂停增加。具体而言，HP 1B和HP 1C的共定位与最高水平的聚合酶暂停和基因表达相关。HP 1无效突变体的分析表明，这些蛋白质协调活动在转录起始位点调节转录。HP 1B或HP 1C的消耗改变了由HP 1家族成员结合的蛋白质编码基因的表达。我们的数据拓宽了对HP 1a转录激活机制的理解，并强调需要考虑特定的蛋白质-蛋白质相互作用，而不是更广泛的染色质背景，以预测HP 1在转录起始位点的影响。
Drosophila Heterochromatin Protein 1a (HP1a) is essential for heterochromatin formation and is involved in transcriptional silencing. However, certain loci require HP1a to be transcribed. One model posits that HP1a acts as a transcriptional silencer within euchromatin while acting as an activator within heterochromatin. However, HP1a has been observed as an activator of a set of euchromatic genes. Therefore, it is not clear whether, or how, chromatin context informs the function of HP1 proteins. To understand the role of HP1 proteins in transcription, we examined the genome-wide binding profile of HP1a as well as two other Drosophila HP1 family members, HP1B and HP1C, to determine whether coordinated binding of these proteins is associated with specific transcriptional outcomes. We found that HP1 proteins share many of their endogenous binding targets. These genes are marked by active histone modifications and are expressed at higher levels than nontarget genes in both heterochromatin and euchromatin. In addition, HP1 binding targets displayed increased RNA polymerase pausing compared with nontarget genes. Specifically, colocalization of HP1B and HP1C was associated with the highest levels of polymerase pausing and gene expression. Analysis of HP1 null mutants suggests these proteins coordinate activity at transcription start sites to regulate transcription. Depletion of HP1B or HP1C alters expression of protein-coding genes bound by HP1 family members. Our data broaden understanding of the mechanism of transcriptional activation by HP1a and highlight the need to consider particular protein–protein interactions, rather than broader chromatin context, to predict impacts of HP1 at transcription start sites.