BBS Faculty Member - Kami Ahmad

Kami Ahmad

Department of Biological Chemistry and Molecular Pharmacology

Harvard Medical School
BCMP Bldg. C, Room 204
240 Longwood Ave.
Boston, MA 02115
Tel: 617-432-0588
Fax: 617-738-0516
Email: kami_ahmad@hms.harvard.edu



Histone variants and biological properties of chromatin
My work focuses on the functions of histones and chromatin in processes that use DNA as a template. Eukaryotes package their genomes into nucleosomes, where DNA is tightly wrapped around an octamer of core histones. Nucleosomes are formidable barriers to proteins that must access DNA, yet transcription, replication, and repair occurs efficiently in vivo, in ways that are poorly understood. Nucleosomes must be disrupted during these processes, and a crucial aspect of chromatin-based processes must be to promote disruption and then reassemble nucleosomes. The lab addresses the components and mechanisms of chromatin assembly using genetic systems in Drosophila.

One area of research focuses on the functions of histones themselves. Histones are extremely well-conserved throughout eukaryotes, but some variants are now known to be functionally distinct. The histone H3 variant H3.3 is targeted to actively transcribed chromatin, and our experiments imply the existence of a specialized assembly pathway that continually rebuilds nucleosomes after chromatin has been disrupted by transcriptional activity. We are studying mutations of H3.3 to ask if this variant potentiates transcription in active chromatin.

Our second interest is the mechanism of heterochromatic gene silencing. Highly repetitive regions of the genome form heterochromatin, which is associated with specific histone and chromatin modifications. Chromosomal rearrangements that juxtapose a gene to heterochromatin often repress expression. An unexplained feature of heterochromatic silencing is that it is always mosaic, and a gene can suddenly switch between active and silent states. Using a defined silencing system with a GAL4-dependent reporter gene allows us to vary the timing and activity of the promoter, which proves to have a strong effect on mosaicism. This work also shows that silent and active promoters can coexist in a small interval. Our hypothesis is that heterochromatin inhibits the disruption of nucleosomes around promoters, thus blocking transcription. Current experiments are testing this model.



Last Update: 5/28/2013



Publications

B.E. Schwartz and K. Ahmad (2005). Transcription triggers deposition and removal of the histone variant H3.3. Genes & Development 19, 804-814.

K. Ahmad and S. Henikoff (2002c). Epigenetic effects of nucleosome dynamics. Cell 111:281-284.

K. Ahmad and S. Henikoff (2002a). The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly. Molecular Cell 9:1191-1200.

K. Ahmad and S. Henikoff (2001). Modulation of a transcription factor counteracts heterochromatic gene-silencing in Drosophila. Cell 104:839-847.



© 2013 by the President and Fellows of Harvard College