Poster abstracts
Poster number 32 submitted by Liudmila Popova
Epigenetic regulation of nuclear lamina-associated heterochromatin domains by HAT1 and the acetylation of newly synthesized histones
Liudmila Popova (MCBD), Prabakaran Nagarajan, Callie M. Lovejoy (Department of Biological Chemistry and Pharmacology, The Ohio State University), Benjamin Sunkel (Nationwide Childrens Research Institute), Michael A. Freitas (Department of Cancer Biology and Genetics), Benjamin Stanton (Nationwide Childrens Research Institute), Mark R. Parthun (Department of Biological Chemistry and Pharmacology, The Ohio State University)
Abstract:
When eukaryotic cells divide, not all of the information necessary for proper functioning of daughter cells is encoded in the primary DNA sequence of their genomes. Regulatory information, such is chemical modifications to histone proteins, is inherited epigenetically during cell division. In mammals, faithful transmission of epigenetic information is essential for maintenance of cell identity, genome integrity, and control of cell proliferation.
During DNA replication, parental histones are recycled and deposited behind the replication fork and newly synthesized histones are delivered to sites of replication via the pathway of replication-coupled chromatin assembly. Histone Acetyltransferase 1 (Hat1) plays an important role in replication-coupled chromatin assembly by acetylating lysines 5 and 12 in the tail of the newly synthesized histone H4.
Here, we report that HAT1 is a key regulator of the epigenetic inheritance of chromatin states and genome architecture. HAT1 is a global negative regulator of H3K9me2 and K9me3. ATAC-Seq analysis demonstrates that HAT1 regulates accessibility of specific chromosomal domains, termed HAT1-dependent accessibility domains (HADs). HADs range in size from 0.1 to 10 Mb, are AT-rich, gene poor and heterochromatic. HADs correspond to regions of the genome with the highest density of H3 K9 methylation. HADs also display a high degree of overlap with Lamina-Associated Domains suggesting that HAT1 and acetylation of newly synthesized histones regulate the association between heterochromatin and the nuclear lamina following DNA replication. We also propose a model for the epigenetic regulation of histone H3 methylation by HAT1 and newly synthesized histone acetylation and for the role of histone modification dynamics in the association of nascent chromatin with the nuclear lamina.
Keywords: Hat1, Epigenetics, Nuclear Lamina-Heterochromatin Interactions