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HAT-HDAC System in Asthma

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Genomic Approach to Asthma

Part of the book series: Translational Bioinformatics ((TRBIO,volume 12))

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Abstract

Diverse biological processes, including regulation of inflammatory gene expression, DNA damage repair, and cell growth, are balanced by modifications on histones such as acetylation (HAT) and deacetylation (HDAC). HAT/HDAC has recently emerged as a critical regulator of inflammatory disease.

HATs are enzymes that specifically add an acetyl group to the lysine amino acids within a conserved motif on histone proteins resulting in loosening the DNA from histones, and driving inflammatory gene expression. HDACs, grouped in four classes, suppress the inflammatory gene expression by reversing the reaction catalyzed by HATs.

The chapter is focusing on the potential asthma-relief effects of HAT and/or HDAC compounds. Recently, more specific HAT inhibitors (HATi) and HDAC inhibitors (HDACi) have been described. This can now serve as perfect tools to study the function of HATs and HDACs in model systems of asthma. Oral or inhaled corticosteroids are widely used as maintenance therapy for asthmatics. However, its disease control effect is diminished in asthma smokers and severe asthma patients. Reduced responsiveness to the anti-inflammatory effects of corticosteroids is a major barrier to effective management of asthma in smokers and patients with severe asthma. Reduced expression of HDAC2 may be involved in the molecular mechanism of corticosteroid insensitivity in asthmatics. We further investigate how HDAC2 play a role in glucocorticoid (GC) insensitivity in asthmatics and find it is a potential target to reverse GC activity.

Although the precise mechanisms of HAT/HDAC are still controversial, their roles as potential drug targets for asthma have been represented. It should also be noted the existence of multiple subtypes of HDAC/HAT adds to the complexity of their biological effect in asthma. This remains a hot area in today’s asthma research.

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Authors and Affiliations

  1. Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China

    Xiaoru Sun

  2. Respiratory Division of Zhongshan Hospital, Shanghai Institute of Respiratory Diseases, Fudan University, Shanghai, China

    Xiaoru Sun

  3. Shanghai Respiratory Research Institute, Respiratory Division of Zhongshan Hospital, Fudan University, Shanghai, China

    Zhihong Chen

  4. Zhongshan Hospital Institute of Clinical Science, Shanghai Medical School, Fudan University, Shanghai, China

    Xiangdong Wang

  5. Shanghai Institute of Clinical Bioinformatics, Fudan University, Shanghai, China

    Xiangdong Wang

Authors
  1. Xiaoru Sun
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  2. Zhihong Chen
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  3. Xiangdong Wang
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Correspondence to Xiangdong Wang .

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Editors and Affiliations

  1. Zhongshan Hospital Institute of Clinical Science, Shanghai Medical School Fudan University, Shanghai, China

    Xiangdong Wang

  2. Shanghai Respiratory Research Institute, Respiratory Division of Zhongshan Hospital, Fudan University, Shanghai, China

    Zhihong Chen

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Sun, X., Chen, Z., Wang, X. (2018). HAT-HDAC System in Asthma. In: Wang, X., Chen, Z. (eds) Genomic Approach to Asthma. Translational Bioinformatics, vol 12. Springer, Singapore. https://doi.org/10.1007/978-981-10-8764-6_12

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