Biomedical subjects

Hannah J Whiteman

Publications and source records attributed to Hannah J Whiteman.

2 recordsLinked to original sources

PubMed2006

RUNX expression and function in human B cells.

RUNX1 and RUNX3 are expressed at many stages of B-cell differentiation, suggesting that they play a role in the development and functions of this lineage. Transgenic mice lacking expression of RUNX1 or the RUNX protein-binding partner, CBFbeta, have defective B-cell development, with differentiation blocked at an early stage. Specific knockout of RUNX1 in adult hematopoietic cells also caused a decrease in the number of mature B cells, supporting a role for RUNX1 in both developmental and adult hematopoiesis. Furthermore, RUNX proteins have been shown to regulate several B-cell-specific genes and play an important role in TGF-beta-induced immunoglobulin class switching to IgA. The importance of RUNX1 in B-cell development is additionally demonstrated by its dysregulation in the t(12;21) translocation, which is the most frequent translocation found in acute lymphocytic leukemia. Epstein Barr virus immortalized human B lymphoblastoid cell lines express RUNX3, and cross-regulation of RUNX1 by RUNX3 occurs in these cells. Knockdown of RUNX3 in these cells induces RUNX1 expression and inhibits cell proliferation, directly showing that RUNX proteins can regulate B-cell growth.

B-Lymphocytes↗

PubMed2005

Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells.

RUNX transcription factors are important in development and in numerous types of human cancer. They act as either transcriptional activators or repressors and can be proto-oncogenes or tumour suppressors. Understanding their regulation and interaction may explain how RUNX factors contribute to such different and often opposing biological processes. We show that RUNX3 regulates RUNX1 expression, contributing to the mutually exclusive expression of RUNX3 and RUNX1 in human B lymphoid cell lines. RUNX3 repressed the RUNX1 P1 promoter by binding specifically to conserved RUNX sites near the transcription start of the promoter. siRNA inhibition of RUNX3 in lymphoblastoid cells resulted in increased RUNX1 expression, indicating that continuous expression of physiological levels of RUNX3 is required to maintain repression. Furthermore, expression of RUNX3 was required for efficient proliferation of B cells immortalized by Epstein-Barr virus. Cross-regulation between different RUNX family members is therefore a means of controlling RUNX protein expression and must now be considered in the interpretation of pathological changes due to loss of RUNX3 tumour suppressor function or following gene duplication or translocation events.

B-Lymphocytes↗