哥伦比亚大学的Laura F. Landweber研究组与普林斯顿大学的Tom W. Muir研究组合作发现DNA 6mA甲基转移酶复合物及其对染色质组装的影响。相关论文于2019年6月发表在《细胞》杂志上。

DNA N6-腺嘌呤甲基化（6mA）修饰最近在从单细胞到多细胞的多种真核生物中被发现。

在这项工作中，研究人员报道了纤毛虫中的一个DNA 6mA甲基转移酶复合物，被命名为MTA1c。这个复合物含有2个MT-A70蛋白以及两个具有homeobox-like结构域的DNA结合蛋白，能够特异性甲基化双链DNA。在尖毛虫（纤毛虫的一种）中破坏催化亚基MTA1能够导致全基因组的6mA缺失并消除保守的ApT二甲基化模体（motif）。尖毛虫在完成性周期生长过程中，MTA1的表达也同样呈周期性变化，但缺失MTA1的突变体则无法完成这一周期。研究人员进一步通过体外重组完整的尖毛虫染色体发现，6mA修饰会阻碍核小体的占位。6mA的丰度越高越阻碍核小体的包裹，并且不依赖于DNA的序列。而染色质重塑复合物ACF能够拮抗这一效果。因此，这项工作鉴定到了一个负责DNA 6mA甲基转移酶，并定义了6mA修饰在染色质组装中扮演的角色。

附：英文原文

Title: Identification of a DNA N6-Adenine Methyltransferase Complex and Its Impact on Chromatin Organization

Author: Leslie Y. Beh, Galia T. Debelouchina, Derek M. Clay, Robert E. Thompson, Kelsi A. Lindblad, Elizabeth R. Hutton, John R. Bracht, Robert P. Sebra, Tom W. Muir, Laura F. Landweber

Issue&Volume: Jun 13, 2019 Volume 177Issue 7 

Abstract: DNA N6-adenine methylation (6mA) has recently been described in diverse eukaryotes, spanning unicellular organisms to metazoa. Here, we report a DNA 6mA methyltransferase complex in ciliates, termed MTA1c. It consists of two MT-A70 proteins and two homeobox-like DNA-binding proteins and specifically methylates dsDNA. Disruption of the catalytic subunit, MTA1, in the ciliate Oxytricha leads to genome-wide loss of 6mA and abolishment of the consensus ApT dimethylated motif. Mutants fail to complete the sexual cycle, which normally coincides with peak MTA1 expression. We investigate the impact of 6mA on nucleosome occupancy in vitro by reconstructing complete, full-length Oxytricha chromosomes harboring 6mA in native or ectopic positions. We show that 6mA directly disfavors nucleosomes in vitro in a local, quantitative manner, independent of DNA sequence. Furthermore, the chromatin remodeler ACF can overcome this effect. Our study identifies a diverged DNA N6-adenine methyltransferase and defines the role of 6mA in chromatin organization.

DOI: https://doi.org/10.1016/j.cell.2019.04.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30447-7