Urban Jennifer, Kuzu Guray, Bowman Sarah, Scruggs Benjamin, Henriques Telmo, Kingston Robert, Adelman Karen, Tolstorukov Michael, Larschan Erica
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
PLoS One. 2017 Oct 27;12(10):e0186855. doi: 10.1371/journal.pone.0186855. eCollection 2017.
The essential process of dosage compensation is required to equalize gene expression of X-chromosome genes between males (XY) and females (XX). In Drosophila, the conserved Male-specific lethal (MSL) histone acetyltransferase complex mediates dosage compensation by increasing transcript levels from genes on the single male X-chromosome approximately two-fold. Consistent with its increased levels of transcription, the male X-chromosome has enhanced chromatin accessibility, distinguishing it from the autosomes. Here, we demonstrate that the non-sex-specific CLAMP (Chromatin-linked adaptor for MSL proteins) zinc finger protein that recognizes GA-rich sequences genome-wide promotes the specialized chromatin environment on the male X-chromosome and can act over long genomic distances (~14 kb). Although MSL complex is required for increasing transcript levels of X-linked genes, it is not required for enhancing global male X-chromosome chromatin accessibility, and instead works cooperatively with CLAMP to facilitate an accessible chromatin configuration at its sites of highest occupancy. Furthermore, CLAMP regulates chromatin structure at strong MSL complex binding sites through promoting recruitment of the Nucleosome Remodeling Factor (NURF) complex. In contrast to the X-chromosome, CLAMP regulates chromatin and gene expression on autosomes through a distinct mechanism that does not involve NURF recruitment. Overall, our results support a model where synergy between a non-sex-specific transcription factor (CLAMP) and a sex-specific cofactor (MSL) creates a specialized chromatin domain on the male X-chromosome.
剂量补偿的基本过程对于平衡雄性（XY）和雌性（XX）之间X染色体基因的表达是必需的。在果蝇中，保守的雄性特异性致死（MSL）组蛋白乙酰转移酶复合物通过将单个雄性X染色体上基因的转录水平提高约两倍来介导剂量补偿。与其转录水平的增加相一致，雄性X染色体具有增强的染色质可及性，这使其与常染色体区分开来。在这里，我们证明了一种非性别特异性的CLAMP（MSL蛋白的染色质连接衔接子）锌指蛋白，它能在全基因组范围内识别富含GA的序列，促进雄性X染色体上的特殊染色质环境，并且可以在长基因组距离（约14 kb）上发挥作用。虽然MSL复合物是增加X连锁基因转录水平所必需的，但它不是增强雄性X染色体整体染色质可及性所必需的，而是与CLAMP协同作用，以促进其最高占据位点处的可及染色质构象。此外，CLAMP通过促进核小体重塑因子（NURF）复合物的募集来调节强MSL复合物结合位点处的染色质结构。与X染色体不同，CLAMP通过一种不涉及NURF募集的独特机制来调节常染色体上的染色质和基因表达。总体而言，我们的结果支持一种模型，即非性别特异性转录因子（CLAMP）和性别特异性辅因子（MSL）之间的协同作用在雄性X染色体上创建了一个特殊的染色质结构域。
