真核生物的基因组折叠为高度有序的三维结构，然而，三维基因组结构形成的分子机制及其对转录调控的影响目前仍未被很好地理解。染色质区室（A/B compartment）是不同物种中普遍存在的染色质高维结构, 使得不同转录活性的基因组区域在空间上相互分离。申请人在线虫中的前期研究表明，异染色质相关的H3K9甲基化等组蛋白修饰可能通过多层次的分子机制，调控异染色质在三维空间的相互作用及核膜定位，进而驱动染色质区室的形成。我们进一步发现染色质区室的形成可能对机体应激反应中的转录调控有重要影响。我们在本课题中将利用多种异染色质缺陷的线虫模型，结合遗传学、细胞生物学，以及Hi-C等基因组学手段对染色质区室形成的分子机制进行研究，并对染色质区室在应激反应中影响转录调控的机制进行探索，以期揭示基因组空间组织的一般性机制，并促进对衰老、应激等重要生命过程中基因组调控规律的理解。

Interphase chromosomes are highly organized, but the mechanisms that establish higher order structures and their importance for transcription are not well understood. Transcriptionally active regions and inactive regions segregate from each other to form distinct A and B compartments. While genome compartmentalization is a highly conserved feature of eukaryotic genome organization, its underlying mechanisms and functional importance remain elusive. The patterns of genome compartmentalization correlate strongly with epigenetic landscape, implying important roles of epigenetic modifications in genome organization. Here we use Caenorhabditis elegans as a model to dissect the roles of heterochromatin markers in genome organization. we discovered H3K9me promotes the formation and segregation of genome compartments in C. elegans. We showed that H3K9me regulates genome compartmentalization partially through anchoring heterochromatic regions to the nuclear periphery, revealing the role of radial positioning of genomic regions in genome organization. Furthermore, we discovered the loss of H3K9me and the weakening of compartmentalization results in increased thermosensitivity, suggesting genome compartmentalization may be important for proper gene expression during stress response. We will further investigate how heterochromatin markers establish and regulate genome compartmentalization and how genome compartmentalization facilitates stress-induced transcriptional response. The proposed studies will promote the understanding of the relationship between genome architecture and transcription regulation during stress response and aging.