Shaukat Ammad, Khan Muhammad Haider Farooq, Ahmad Hina, Umer Zain, Tariq Muhammad
Epigenetics and Gene Regulation Laboratory, Department of Biology, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan.
Front Cell Dev Biol. 2021 Sep 28;9:740866. doi: 10.3389/fcell.2021.740866. eCollection 2021.
CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In , CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in . Here, we report a previously unknown interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.
CREB结合蛋白(CBP)是一种多功能转录共激活因子,它与多种转录因子相互作用,并作为组蛋白乙酰转移酶发挥作用。在[具体情况]中,CBP介导的组蛋白H3赖氨酸27(H3K27ac)乙酰化是由三胸蛋白家族(trxG)调控的基因激活的已知标志。最近,我们发现一种组蛋白激酶Ballchen(BALL)在trxG靶位点与H3K27ac大量共定位,并且是维持[具体情况]中基因激活所必需的。在此,我们报道了BALL与CBP之间一种以前未知的相互作用,这种相互作用正向调节H3K27ac。对BALL和CBP全基因组结合图谱的分析揭示了它们在活跃转录基因上的主要重叠和共定位。我们表明BALL在生化上与CBP相互作用,BALL的缺失导致H3K27ac急剧减少。总之,这些结果证明了BALL与CBP之间以前未知的协同作用,并揭示了在发育过程中维持基因激活所需的一条潜在新途径。