DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines

Dulamsuren Oktyabri; Akihiko Ishimura; Shoichiro Tange; Minoru Terashima; Takeshi Suzuki

doi:10.1016/j.biochi.2016.01.005

DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines

Biochimie. 2016 Apr:123:20-31. doi: 10.1016/j.biochi.2016.01.005. Epub 2016 Jan 16.

Authors

Dulamsuren Oktyabri¹, Akihiko Ishimura², Shoichiro Tange¹, Minoru Terashima¹, Takeshi Suzuki³

Affiliations

¹ Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
² Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan; Molecular Therapeutic Target Research Unit, Institute for Frontier Science Initiative (InFIniti), Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan.
³ Division of Functional Genomics, Cancer Research Institute, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan; Molecular Therapeutic Target Research Unit, Institute for Frontier Science Initiative (InFIniti), Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan. Electronic address: suzuki-t@staff.kanazawa-u.ac.jp.

PMID: 26783998
DOI: 10.1016/j.biochi.2016.01.005

Abstract

DOT1L is a histone H3 lysine 79 (H3K79) methyltransferase mainly implicated in leukemia. Here we analyzed the function of DOT1L in breast cancer cells. The expression of DOT1L was up-regulated in malignant breast cancer tissues. Over-expression of DOT1L significantly increased the sphere formation and the cell migration activities of MCF7 breast cancer cell line. In contrast, knockdown of DOT1L reduced the cell migration activity of MDA-MB-231 breast cancer cell line. BCAT1, which encodes a branched-chain amino acid transaminase, was identified as one of the target genes controlled by DOT1L through the regulation of H3K79 methylation. Mechanistic investigation revealed that BCAT1 might be an important regulator responsible for DOT1L-mediated sphere formation and cell migration in breast cancer cells.

Keywords: Cancer progression; Cell migration; Histone methyltransferase; Sphere formation; Transcriptional regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Cell Line, Tumor
Female
Gene Expression Regulation
Histone-Lysine N-Methyltransferase
Humans
Methylation
Methyltransferases / metabolism*
Neoplasm Metastasis*
Transaminases / genetics*

Substances

DOT1L protein, human
Methyltransferases
Histone-Lysine N-Methyltransferase
BCAT1 protein, human
Transaminases