DNA sequence-dependent epigenetic inheritance of gene silencing and histone H3K9 methylation

Abstract

Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9) is methylated (H3K9me) at heterochromatic domains. These domains can be epigenetically inherited when <i>epe1⁺</i> , encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in <i>epe1⁺</i> cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state. We show that in <i>epe1⁺</i> cells, in addition to sequence-independent mechanisms that propagate H3K9me, epigenetic inheritance of silencing requires binding sites for sequence-dependent activating transcription factor (ATF)-adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB) family transcription factors within their native chromosomal context. Thus, specific DNA sequences contribute to cis inheritance of H3K9me and silent epigenetic states.