Bassem Al-Sady, PhD

Asst Professor in Residence
Department of Microbiology and Immunology
+1 415 502-8655
Research Overview: 

Heterochromatin is a specialized protein-nucleic acid composite that silences the activity of genes over large contiguous chromosomal regions, and that has been visualized as a distinct nuclear ultra-structure for almost a century. Remarkably, the mechanisms guiding heterochromatin spreading along the chromosome and precise re-assembly every cell cycle remain obscure, although they critically relate to the potential of heterochromatin to epigenetically regulate genomic loci.

Excitingly, it is now appreciated that heterochromatin spreading plays a key role in the genome partitioning process that shapes cell fate. Heterochromatin exists in small regions, presumably around nucleation sites in embryonic stem cells (ESCs) that expand differentially depending on the lineage track. Once the spreading reaction has completed, the new pattern is stably adopted. How heterochromatin spreading from small nucleation sites in ESCs is developmentally regulated to drive lineage fates, or how lineages decisions direct differential spreading is completely unknown.

The lab aims to elucidate critical mechanisms that underlie normal formation of epigenetic states and their stable inheritance and developmental regulation. To address these mechanisms, we are using two broad approaches, biochemical reconstitution of heterochromatin assembly and single cell analysis of the spreading reaction in live cells.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Mechanisms of formation and maintenance of epigenetic elements
Mentorship Development: 

2/2021 - Three Truths & Three Tries: Facing & Overcoming Critical Social Justice Challenges at the Micro, Mezzo & Macro Levels



Local chromatin context regulates the genetic requirements of the heterochromatin spreading reaction.

PLoS genetics

Greenstein RA, Ng H, Barrales RR, Tan C, Braun S, Al-Sady B

The histone chaperone FACT facilitates heterochromatin spreading by regulating histone turnover and H3K9 methylation states.

Cell reports

Murawska M, Greenstein RA, Schauer T, Olsen KCF, Ng H, Ladurner AG, Al-Sady B, Braun S

Heterodimerization of H3K9 histone methyltransferases G9a and GLP activates methyl reading and writing capabilities.

The Journal of biological chemistry

Sanchez NA, Kallweit LM, Trnka MJ, Clemmer CL, Al-Sady B

Set1/COMPASS repels heterochromatin invasion at euchromatic sites by disrupting Suv39/Clr4 activity and nucleosome stability.

Genes & development

Greenstein RA, Barrales RR, Sanchez NA, Bisanz JE, Braun S, Al-Sady B