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1.  Class IIa Histone Deacetylases Are Conserved Regulators of Circadian Function* 
The Journal of Biological Chemistry  2014;289(49):34341-34348.
Background: Class IIa HDACs are signal-dependent transcriptional corepressors that regulate cell differentiation programs and liver gluconeogenesis.
Results: HDAC5 influences BMAL1 acetylation and interfering with normal expression levels of class IIa HDACs disrupts circadian rhythms.
Conclusion: Class IIa HDACs regulate the robustness of cellular clocks and behavioral activity rhythms.
Significance: Class IIa HDACs provide a conserved link between circadian clocks and metabolic signaling pathways.
Class IIa histone deacetylases (HDACs) regulate the activity of many transcription factors to influence liver gluconeogenesis and the development of specialized cells, including muscle, neurons, and lymphocytes. Here, we describe a conserved role for class IIa HDACs in sustaining robust circadian behavioral rhythms in Drosophila and cellular rhythms in mammalian cells. In mouse fibroblasts, overexpression of HDAC5 severely disrupts transcriptional rhythms of core clock genes. HDAC5 overexpression decreases BMAL1 acetylation on Lys-537 and pharmacological inhibition of class IIa HDACs increases BMAL1 acetylation. Furthermore, we observe cyclical nucleocytoplasmic shuttling of HDAC5 in mouse fibroblasts that is characteristically circadian. Mutation of the Drosophila homolog HDAC4 impairs locomotor activity rhythms of flies and decreases period mRNA levels. RNAi-mediated knockdown of HDAC4 in Drosophila clock cells also dampens circadian function. Given that the localization of class IIa HDACs is signal-regulated and influenced by Ca2+ and cAMP signals, our findings offer a mechanism by which extracellular stimuli that generate these signals can feed into the molecular clock machinery.
PMCID: PMC4256363  PMID: 25271152
Circadian Rhythm; Clock Gene; Drosophila; Histone Deacetylase (HDAC); Nuclear Translocation
2.  Tissue specific characterisation of Lim-kinase 1 expression during mouse embryogenesis 
Gene expression patterns : GEP  2010;11(3-4):221-232.
The Lim-kinase (LIMK) proteins are important for the regulation of the actin cytoskeleton, in particular the control of actin nucleation and depolymerisation via regulation of cofilin, and hence may control a large number of processes during development, including cell tensegrity, migration, cell cycling, and axon guidance. LIMK1/LIMK2 knockouts disrupt spinal cord morphogenesis and synapse formation but other tissues and developmental processes that require LIMK are yet to be fully determined. To identify tissues and cell-types that may require LIMK, we characterised the pattern of LIMK1 protein during mouse embryogenesis. We showed that LIMK1 displays an expression pattern that is temporally dynamic and tissue-specific. In several tissues LIMK1 is detected in cell-types that also express Wilms’ tumour protein 1 and that undergo transitions between epithelial and mesenchymal states, including the pleura, epicardium, kidney nephrons, and gonads. LIMK1 was also found in a subset of cells in the dorsal retina, and in mesenchymal cells surrounding the peripheral nerves. This detailed study of the spatial and temporal expression of LIMK1 shows that LIMK1 expression is more dynamic than previously reported, in particular at sites of tissue–tissue interactions guiding multiple developmental processes.
PMCID: PMC3407955  PMID: 21167960
Limk; Kidney; Heart; Epithelia-to-mesenchyme transition; Mesenchyme-to-epithelia transition; Eye; Testes

Results 1-2 (2)