Department of Biology, Emory University, Atlanta, GA 30322, USA and Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
Nucleic Acids Res. 2013 Nov;41(20):9274-83. doi: 10.1093/nar/gkt722. Epub 2013 Aug 13.
Brd4 is a double bromodomain protein that has been shown to interact with acetylated histones to regulate transcription by recruiting Positive Transcription Elongation Factor b to the promoter region. Brd4 is also involved in gene bookmarking during mitosis and is a therapeutic target for the treatment of acute myeloid leukemia. The Drosophila melanogaster Brd4 homologue is called Fs(1)h and, like its vertebrate counterpart, encodes different isoforms. We have used ChIP-seq to examine the genome-wide distribution of Fs(1)h isoforms. We are able to distinguish the Fs(1)h-L and Fs(1)h-S binding profiles and discriminate between the genomic locations of the two isoforms. Fs(1)h-S is present at enhancers and promoters and its amount parallels transcription levels. Correlations between the distribution of Fs(1)h-S and various forms of acetylated histones H3 and H4 suggest a preference for binding to H3K9acS10ph. Surprisingly, Fs(1)h-L is located at sites in the genome where multiple insulator proteins are also present. The results suggest that Fs(1)h-S may be responsible for the classical role assigned to this protein, whereas Fs(1)h-L may have a new and unexpected role in chromatin architecture by working in conjunction with insulator proteins to mediate intra- or inter-chromosome interactions.
Brd4 是一种双溴结构域蛋白，已被证明通过招募正转录伸长因子 b 到启动子区域与乙酰化组蛋白相互作用来调节转录。Brd4 还参与有丝分裂中的基因标记，并成为治疗急性髓细胞白血病的治疗靶点。果蝇中的 Brd4 同源物称为 Fs(1)h，与脊椎动物的 Brd4 类似，它编码不同的亚型。我们使用 ChIP-seq 来检查 Fs(1)h 亚型的全基因组分布。我们能够区分 Fs(1)h-L 和 Fs(1)h-S 的结合图谱，并区分两种亚型的基因组位置。Fs(1)h-S 存在于增强子和启动子上，其数量与转录水平平行。Fs(1)h-S 的分布与各种形式的乙酰化组蛋白 H3 和 H4 之间的相关性表明其对 H3K9acS10ph 的结合具有偏好性。令人惊讶的是，Fs(1)h-L 位于基因组中存在多个绝缘子蛋白的位置。结果表明，Fs(1)h-S 可能负责该蛋白的经典作用，而 Fs(1)h-L 可能通过与绝缘子蛋白协同作用来介导染色体内或染色体间相互作用，从而在染色质结构中发挥新的、意想不到的作用。
