Science

Research Areas

I am broadly interested in how chromosomes encode and transmit biological information across cell divisions and generations. Currently, my work focuses on the molecular basis of the inheritance of chromatin states for genome maintenance and cell fate decisions. By integrating genetic, biochemical, microscopic, and structural approaches, I aim to uncover the general principles governing chromosome-based memory for development and evolution.

Chromatin dynamics and epigenetic inheritance

Faithful inheritance of chromatin states is essential for preserving gene expression patterns and genome integrity. I am interested in understanding the molecular mechanisms of how chromatin maintains its epigenetic information during essential biological processes, including chromosomal duplication, transcription, and other large-scale chromatin remodeling events.

My Ph.D. thesis work uncovered a novel function of replication checkpoint factor Mrc1/CLASPIN in epigenetic inheritance by distributing parental histones to both daughter DNA strands. Mechanistically, Mrc1/CLASPIN contains a conserved histone H3-H4 tetramer binding domain that anchors at the center of the replication fork. Together with other replisome-associated histone chaperones, my thesis work suggests that the replisome contains multiple intermediate sites for parental histone recycling. (Yu et al., PMID: 39094570, 2024, Yu and Moazed, PMID: 42008660, 2026).

Parental histone distribution site (D site) [Modelled by PDB: 8XGC (cryo-EM) and ma-dm-hisrep-263 (AlphaFold)].

Genome maintenance across species

Repetitive DNA, such as satellite DNA (satDNA) and transposable elements (TEs), are widely present genetic elements in the eukaryotic genome. Repetitive DNA comprises a substantial fraction of both the fruit fly Drosophila melanogaster genome (~20% satDNA, >20% TE) and human genome (~6% satDNA, 45% TEs). Most repetitive DNA is assembled into constitutive heterochromatin and is transcriptionally silent. Although decades of studies have shown that pericentric repeats and their associated heterochromatin contribute to centromere formation and kinetochore assembly, it remains unknown whether repetitive DNA has been integrated into other cellular processes that could be critical for its retention during evolution.

One of the major goals of my postdoctoral research is to understand how repetitive DNA-binding proteins adapt to the evolution of repetitive DNA to facilitate genome maintenance across generations and species. Using the Drosophila male germline as the model system, I am interested in identifying novel roles of repetitive DNA in transmitting genetic material across generations and species.

Drosophila spermatogenesis. The diagram illustrates the key developmental stages of Drosophila male germline.

Chromosome segregation and cell fate decision

Adult stem cells undergo asymmetric cell division to generate a self-renewing stem cell and a differentiating cell. A fundamental unsolved question is how two daughter cells can adopt distinct cell fates during this process.

During asymmetric divisions of the Drosophila male germline stem cell, sister chromatids undergo non-random segregation. This observation suggests that two genetically identical sister chromatids are created differently, potentially priming for cell fate decisions. However, it remains unclear how the differences between sister chromatids are established and recognized by germline stem cells. Another goal of my postdoc work is to understand the molecular basis underlying non-random sister chromatid segregation (NRSS) and its role in cell fate specification and differentiation.

Non-random sister chromatid segregation in Drosophila male germline stem cells.

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