N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation

C. elegans heritably adapts to P. vranovensis infection via a mechanism that requires the cysteine synthases cysl-1 and cysl-2

“…In some cases, the effects of parental stress on offspring have been reported to be intergenerational and only last a single generation 1 . In other cases, the effects of parental stress on offspring have been reported to persist transgenerationally and thus affect descendants several generations later 5, 8, 21 . To test whether exposure to BIGb446 had any transgenerational effects on immunity we fed adult animals BIGb446 for 24 hours and assayed the response of progeny two generations later.…”

“…2a), indicating that the effects of parental exposure to BIGb446 only last a single generation under these conditions. Some studies of the effects of parental environment on offspring have found that consecutive exposure of multiple generations of animals to the same stress can enhance adaptation to stress in descendants 5 . We therefore tested whether the exposure of five consecutive generations (P0, F1, F2, F3, and F4) of animals to BIGb446 could enhance progeny (F5) survival in response to BIGb446 but found that this was not the case (Fig.…”

“…Multiple signaling pathways and epigenetic modifiers have been proposed to mediate heritable and transgenerational responses to environmental stress. We tested whether mutations in any factors previously reported to be involved heritable or transgenerational responses to stress were required for C. elegans heritable adaptation to BIGb446 including small RNA mediated pathways ( hrde-1 22 , prg-1 8 ), H3K9 methylation ( set-32 23 and met-2 4 ), H3K4 methylations ( set-2, wdr-5.1, spr-5 ) 5, 21 , DNA adenosine methylation ( damt-1 ) 5 , and the RAS/ERK signaling pathway ( lin-45 ) 1 . We found that none of these factors were required for C. elegans adaptation to BIGb446 (Fig.…”

“…Intergenerational and transgenerational responses to environmental stress have been reported in evolutionarily diverse organisms 1–7 . These studies investigated a variety of types of stresses ranging from osmotic stress 1 , to mitochondrial stress 5 , to pathogen infection 8 . In each case, parental exposure to stress appeared to prime offspring to respond to a similar stress.…”

CG14906 (mettl4) mediates m6A methylation of U2 snRNA inDrosophila

“…METTL4 is a member of the MT-A70-like protein family, which is conserved during evolution ( Fig.1a) [2]. Previous studies suggested that METTL4 regulates DNA 6mA in vivo and therefore is a candidate DNA m6A methyltransfease [3][4][5]. However, the enzymatic activity of METTL4 in vitro has not been demonstrated.…”