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Ge, K.

Publications and source records attributed to Ge, K..

3 recordsLinked to original sources

Hypothalamic transcriptome analysis reveals the neuroendocrine mechanisms in controlling broodiness of Muscovy duck (Cairina moschata)

Broodiness, one of the maternal behaviors and instincts for natural breeding in birds, is an interesting topic in reproductive biology. Broodiness in poultry is characterized by persistent nesting, usually associated with cessation of egg laying. The study of avian broodiness is essential for bird conservation breeding and commercial poultry industry. In this study, we examined the hypothalamus transcriptome of Muscovy duck in three reproductive stages, including egg-laying anaphase (LA), brooding prophase (BP) and brooding metaphase (BM). Differences in gene expression during the transition from egg-laying to broodiness were examined, and 155, 379, 292 differently expressed genes (DEGs) were obtained by pairwise comparisons of LA-vs-BP, LA-vs-BM and BP-vs-BM, respectively (fold change[&ge;] 1.5, P < 0.05). Gene Ontology Term (GO) enrichment analysis suggested a possible role of oxidative stress in the hypothalamus might invoke reproductive costs that potentially change genes expression. KEGG analysis revealed glutamatergic synapse, dopaminergic synapse, serotonergic synapse and GABAergic synapse pathway were significantly enriched, and regulator genes were identified. Eight gene expression patterns were illustrated by trend analysis and further clustered into three clusters. Additional six hub genes were identified through combining trend analysis and protein-protein interaction (PPI) analysis. Our results suggested that the cyclical mechanisms of reproductive function conversion include effects of oxidative stress, biosynthesis of neurotransmitters or their receptors, and interactions between glucocorticoids and thyroid hormones and regulatory genes. These candidate genes and biological pathways may be used as targets for artificial manipulation and marker-assisted breeding in the reproductive behavior.

animal behavior and cognition

H3.3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development

Histone H3K4 mono-methyltransferases MLL3 and MLL4 (MLL3/4) are required for enhancer activation during cell differentiation, though the mechanism is incompletely understood. To address MLL3/4 enzymatic activity in enhancer regulation, we have generated two mouse lines: one expressing H3.3K4M, a lysine-4-to-methionine (K4M) mutation of histone H3.3 that inhibits H3K4 methylation, and the other carrying conditional double knockout of MLL3/4 enzymatic SET domains. Expression of H3.3K4M in lineage-specific precursor cells depletes H3K4 methylation and prevents adipogenesis and adipose tissue development. Mechanistically, H3.3K4M prevents enhancer activation in adipogenesis by destabilizing MLL3/4 proteins but not other Set1-like H3K4 methyltransferases. Notably, deletion of the enzymatic SET domain of MLL3/4 in lineage-specific precursor cells mimics H3.3K4M expression and prevents adipose tissue development. Interestingly, destabilization of MLL3/4 by H3.3K4M in adipocytes does not affect adipose tissue maintenance and function. Together, our findings indicate that H3.3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development.

molecular biology

Histone H3 Lysine 4 methyltransferases MLL3 and MLL4 Modulate Long-range Chromatin Interactions at Enhancers

Regulation of gene expression in mammalian cells depends on long-range chromatin interactions between enhancers and promoters. Currently, the exact mechanisms that connect distal enhancers to their specific target promoters remain to be fully elucidated. Here we show that the histone H3 Lysine 4 monomethylation (H3K4me1) writer proteins MLL3 and MLL4 (MLL3/4) play an active role in this process. We demonstrate that in differentiating mouse embryonic stem cells, MLL3/4-dependent deposition of H3K4me1 at enhancers correlates with increased levels of chromatin interactions, whereas loss of MLL3/4 leads to greatly reduced frequencies of chromatin interactions and failure of lineage-specific gene expression programs. We further show that H3K4me1 facilitates recruitment of the Cohesin complex to chromatin in vitro and in vivo, providing a potential mechanism for MLL3/4 to promote chromatin looping. Taken together, our results support an active role for MLL3/4 in modulating chromatin organization at enhancers in mammalian cells.

genomics