| First Author | Huang C | Year | 2014 |
| Journal | Blood | Volume | 123 |
| Issue | 7 | Pages | 1012-20 |
| PubMed ID | 24277074 | Mgi Jnum | J:208712 |
| Mgi Id | MGI:5564856 | Doi | 10.1182/blood-2013-07-518605 |
| Citation | Huang C, et al. (2014) Cooperative transcriptional repression by BCL6 and BACH2 in germinal center B-cell differentiation. Blood 123(7):1012-20 |
| abstractText | The transcriptional repressors BCL6 and BACH2 are crucial regulators of germinal center (GC) B-cell fate, and are known to interact and repress transcription of PRDM1, a key driver of plasma cell differentiation. How these factors cooperate is not fully understood. Herein, we show that GC formation is only minimally impaired in Bcl6(+/-) or Bach2(+/-) mice, although double heterozygous Bcl6(+/-)Bach2(+/-) mice exhibit profound reduction in GC formation. Splenic B cells from Bcl6(+/-) Bach2(+/-) mice display accelerated plasmacytic differentiation and high expression of key plasma cell genes such as Prdm1, Xbp1, and CD138. Chromatin immunoprecipitation sequencing revealed that in B cells, BACH2 is mostly bound to genes together with its heterodimer partner MAFK. The BACH2-MAFK complex binds to sets of genes known to be involved in the GC response, 60% of which are also targets of BCL6. Approximately 30% of BACH2 peaks overlap with BCL6, including cis-regulatory sequences of the PRDM1 gene. BCL6 also modulates BACH2 protein stability and their protein levels are positively correlated in GC B cells. Therefore, BCL6 and BACH2 cooperate to orchestrate gene expression patterning in GC B cells through both transcriptional and biochemical mechanisms, which collectively determine the proper initiation and timing of terminal differentiation. |
