Disease relevance of Bcl11b

• Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas [1].

High impact information on Bcl11b

• The gene Bcl11b, which encodes zinc finger proteins, and its paralog, Bcl11a, are associated with immune-system malignancies [2].
• In addition, we saw profound apoptosis in the thymus of neonatal Bcl11b-/- mice [2].
• Bcl11b is required for differentiation and survival of alphabeta T lymphocytes [2].
• Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl11b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that we identified central genetic determinants of the CSMN population [3].
• Most strikingly, Ctip2, a transcription factor required for the formation of the corticospinal tract, was not expressed in the Fezl-deficient cortex [4].

Biological context of Bcl11b

• Allelic loss (LOH) mapping and sequence analysis were conducted for gamma-ray induced mouse thymic lymphomas and a novel tumor suppressor gene, Rit1/Bcl11b, on chromosome 12 was isolated [1].
• No DP thymocytes were detected in thymocytes of adoptive transfer experiments in scid mice that were derived from p53(-/-)Bcl11b(-/-) precursors but ISP thymocytes increased in the proportion and in the cell number approximately three times higher than those from Bcl11b(-/-) precursors [5].
• One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility [6].
• Because this impairment may be due to chromatin accessibility, we have examined histone H3 acetylation in Bcl11b(-/-) DN3 cells using chromatin immunoprecipitation assay [7].
• Bcl11b(-/-) DN3 thymocytes showed normal DNA rearrangements between Dbeta and Jbeta segments but limited DNA rearrangements between Vbeta and DJbeta without effect of distal or proximal positions [7].

Anatomical context of Bcl11b

• Introduction of Rit1 into HeLa cells lacking Rit1 expression suppressed cell growth [1].
• Outside the CNS, both genes exhibited differential expression within the facial mesenchyme at 12.5 d.p.c., and CTIP2 was selectively expressed from day 12.5 onwards in the olfactory epithelium and developing thymus, and to a lesser extent in oral and gut epithelia [8].
• Finally, endogenous SIRT1 and CTIP2 co-purified from Jurkat cell nuclear extracts in the context of a large (1-2 mDa) complex [9].

Associations of Bcl11b with chemical compounds

• CTIP1- and CTIP2-mediated transcriptional repression is insensitive to trichostatin A, an inhibitor of known class I and II histone deacetylases [9].

Other interactions of Bcl11b

• This paper examines the effect of inactivation of p53 on thymocyte development in Bcl11b(-/-) mice that exhibit arrest at the DN3 or (CD4(-)CD8(+)) immature single-positive (ISP) stage [5].
• Analysis of Bcl11b(-/-) DN4 thymocytes showed apoptosis, accompanied with lower expression of anti-apoptotic proteins, Bcl-x(L) and Bcl-2, than wild-type DN4 thymocytes [7].

Analytical, diagnostic and therapeutic context of Bcl11b

• Two distinct methods analyzing chromatin structure using centrifugation and antibodies to modified histone H3: both provide similar chromatin states of the Rit1/Bcl11b gene [10].
• This suggests that the Rit1 intragenic deletions were generated by endogenous illegitimate V(D)J recombinase activity and such aberrant recombination was also detected by nested PCR of DNA from the thymus of unirradiated mice but not of RAG2-deficient mice [11].

References