Histone acetylation is heritable information across generations in spr-2 mutant C. elegans Restricted; Files Only

Abstract

Histone acetylation is an epigenetic marker associated with active transcription that can be used to help maintain cell type specific gene expression. SPR-2 (SET/INHAT in mammals) binds to chromatin and INhibits Histone AcetylTransferase to dampen the acquisition of histone acetylation. Since the acquisition of histone acetylation is a universally conserved mechanism to help maintain gene expression, why would certain cells need to dampen the acquisition of histone acetylation? During the maternal-to-zygotic transition, histone modifications get reprogrammed to prevent the inappropriate maintenance of germline expression in the embryo of the subsequent generation. We find that loss of spr-2 results in the transgenerational accumulation of histone acetylation throughout the genome and sterility across generations (germline mortality). This suggests that SPR-2 dampens acquisition of germline histone acetylation to prevent high levels of histone acetylation which could overwhelm epigenetic reprogramming and be transmitted transgenerationally. These data provide the first evidence that histone acetylation can be stably inherited across generations. Additionally, we show that the accumulation of histone acetylation in spr-2 mutants leads to developmental delay and abnormal chemotaxis behavior, phenotypes that are observed in the corresponding human patients. Based on this overlap in phenotypes, we are using spr-2 mutant C. elegans to understand how inappropriately inherited histone acetylation can give rise to neurodevelopmental defects.

Table of Contents

1.    Chapter I – Introduction

2.    Chapter II – Materials and Methods

3.    Chapter III – Results

4.    Chapter IV – Discussion and Future Directions

5.    Chapter V – References

6.    Chapter VI – Abnormal behavior is reversible in chromatin mutant

7.    Chapter VII – Acknowledgements

 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Evolution and Development Biology, Cell Biology, Genetics
Keyword	Chromatin Ryley Yoo C. elegans Histone acetylation Transgenerational inheritance Epigenetics
Committee Chair / Thesis Advisor	David Katz, Emory University
Committee Members	Victor Corces, Emory University Levi Morran, Emory University

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