The SET domain protein methyltransferases play a critical role in histone modifications and global epigenetic regulations. Recent evidence suggests that some SET domain proteins may have the ability to modify non-histone proteins. The SET domain containing protein 4 (SETD4) was believed to be a non-histone methyltransferase, but no physiological substrate or biological functions of SETD4 has been identified. In this study, we constructed an inducible Setd4 knockout model and investigated the role of Setd4 in radiation sensitivity and tumorigenesis. We found that Setd4 deficient mice were significantly more resistant to radiation-induced hematopoietic syndrome than littermate wild type mice. Using several long-term bone marrow transplantation assays, we found that Setd4 deficient hematopoietic stem cells (HSCs) and progenitor cells (HPCs) have a slight in vivo growth advantage than the wild type cells, but are more sensitive to radiation. We also found that the Setd4 deficient recipient mice have an enhanced ability to engraft transplanted HSCs, suggesting an improved bone marrow niche for the Setd4 deficient animals. Using a radiation-induced thymic lymphoma model, we also found that Setd4 deletion delayed radiation-induced tumorigenesis. Collectively, our study suggests that Setd4 defect can enhance the recovery of radiation-induced bone marrow damage and suppress radiation-induced thymic lymphoma, and that Setd4 is a new gene involved in regulating bone marrow and hematopoietic functions in mice.
Subject (authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
Subject (authority = ETD-LCSH)
Topic
Cancer--Gene therapy
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9129
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (137 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Xing Feng
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
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