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

TitleIdentification of a DNA N6-Adenine Methyltransferase Complex and Its Impact on Chromatin Organization.
Publication TypeJournal Article
Year of Publication2019
AuthorsBeh, LY, Debelouchina, GT, Clay, DM, Thompson, RE, Lindblad, KA, Hutton, ER, Bracht, JR, Sebra, RP, Muir, TW, Landweber, LF
JournalCell
Volume177
Issue7
Pagination1781-1796.e25
Date Published2019 Jun 13
ISSN1097-4172
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.

DOI10.1016/j.cell.2019.04.028
Alternate JournalCell
PubMed ID31104845
PubMed Central IDPMC6570567
Grant ListR01 GM059708 / GM / NIGMS NIH HHS / United States
R01 GM107047 / GM / NIGMS NIH HHS / United States
R01 GM109459 / GM / NIGMS NIH HHS / United States
R35 GM122555 / GM / NIGMS NIH HHS / United States