Unknown

Dataset Information

0

Age-Associated Decrease of the Histone Methyltransferase SUV39H1 in HSC Perturbs Heterochromatin and B Lymphoid Differentiation.


ABSTRACT: The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse HSC, leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. Further, we demonstrate that SUV39H1 is a target of microRNA miR-125b, a known regulator of HSC function, and that expression of miR-125b increases with age in human HSC. Overexpression of miR-125b and inhibition of SUV39H1 in young HSC induced loss of B cell potential. Conversely, both inhibition of miR-125 and enforced expression of SUV39H1 improved the capacity of HSC from elderly individuals to generate B cells. Our findings highlight the importance of heterochromatin regulation in HSC aging and B lymphopoiesis.

SUBMITTER: Djeghloul D 

PROVIDER: S-EPMC4911502 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


The capacity of hematopoietic stem cells (HSC) to generate B lymphocytes declines with age, contributing to impaired immune function in the elderly. Here we show that the histone methyltransferase SUV39H1 plays an important role in human B lymphoid differentiation and that expression of SUV39H1 decreases with age in both human and mouse HSC, leading to a global reduction in H3K9 trimethylation and perturbed heterochromatin function. Further, we demonstrate that SUV39H1 is a target of microRNA mi  ...[more]

Similar Datasets

| S-EPMC1523181 | biostudies-literature
| S-EPMC7762351 | biostudies-literature
| S-EPMC5187760 | biostudies-literature
| S-EPMC4960310 | biostudies-literature
| S-EPMC4876634 | biostudies-literature
| S-EPMC3660348 | biostudies-literature
| S-EPMC5771397 | biostudies-literature
| S-EPMC8609021 | biostudies-literature
| S-EPMC5030085 | biostudies-literature
| S-EPMC5160415 | biostudies-other