Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
Linda Zhang
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, United States
Yung-Hsin Huang
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States
Carina Rosas
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Alexes C Daquinag
Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center, Houston, United States
Anna Guzman
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Raghav Ramabadran
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Chun-Wei Chen
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
Tianpeng Gu
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Sinjini Gupta
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
Laura Ortinau
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Center for Metabolic and Degenerative Disease, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, United States
Dongsu Park
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Center for Metabolic and Degenerative Disease, Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, United States
Aaron R Cox
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States
Rachel E Rau
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, United States
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, United States
Mikhail G Kolonin
Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, United States
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States
DNA Methyltransferase 3 A (DNMT3A) is an important facilitator of differentiation of both embryonic and hematopoietic stem cells. Heterozygous germline mutations in DNMT3A lead to Tatton-Brown-Rahman Syndrome (TBRS), characterized by obesity and excessive height. While DNMT3A is known to impact feeding behavior via the hypothalamus, here we investigated a role in adipocyte progenitors utilizing heterozygous knockout mice that recapitulate cardinal TBRS phenotypes. These mice become morbidly obese due to adipocyte enlargement and tissue expansion. Adipose tissue in these mice exhibited defects in preadipocyte maturation and precocious activation of inflammatory gene networks, including interleukin-6 signaling. Adipocyte progenitor cell lines lacking DNMT3A exhibited aberrant differentiation. Furthermore, mice in which Dnmt3a was specifically ablated in adipocyte progenitors showed enlarged fat depots and increased progenitor numbers, partly recapitulating the TBRS obesity phenotypes. Loss of DNMT3A led to constitutive DNA hypomethylation, such that the DNA methylation landscape of young adipocyte progenitors resemble that of older wild-type mice. Together, our results demonstrate that DNMT3A coordinates both the central and local control of energy storage required to maintain normal weight and prevent inflammatory obesity.