CENP-T Antibody #12494

Modulation of chromatin structure plays a critical role in the regulation of transcription and replication of the eukaryotic genome. The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. In addition to the growing number of post-translational histone modifications regulating chromatin structure, cells can also exchange canonical histones with variant histones that can directly or indirectly modulate chromatin structure (1). CENP-A, also known as the chromatin-associated protein CSE4 (capping-enzyme suppressor 4-p), is an essential histone H3 variant that replaces canonical histone H3 in centromeric heterochromatin (2). The greatest divergence between CENP-A and canonical histone H3 occurs in the amino-terminal tail of the protein, which binds linker DNA between nucleosomes and facilitates proper folding of centromeric heterochromatin (3). The amino-terminal tail of CENP-A is also required for recruitment of other centromeric proteins (CENP-C, hSMC1, hZW10), proper kinetochore assembly, and chromosome segregation during mitosis (4).

CENP-A is regarded as the epigenetic mark of the centromere that persists through cell generations (5). Although its presence is necessary, it is not sufficient for formation of functional kinetochores (6). CENP-T, in complex with CENP-W, has recently been shown to form a histone fold, a structure that is capable of association with DNA, and target DNA to the kinetochore (7). Kinetochore attachment is mediated by a long flexible N-terminal region that has been shown to interact with outer proteins of the kinetochore complex (reviewed in 8). Moreover, the CENP-T-W complex has also been shown to interact with the CENP-S-X dimer, to form a heterotetrameric complex that has structural and potentially functional similarity to canonical histones (8). Since CENP-S-X are conserved kinetochore localized proteins, this new complex has been suggested to be a novel centromeric histone.