Browsing by Author "Shamim, Muhammad S."

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    MCPH1 inhibits Condensin II during interphase by regulating its SMC2-Kleisin interface
    (eLife Sciences Publications Ltd, 2021) Houlard, Martin; Cutts, Erin E.; Shamim, Muhammad S.; Godwin, Jonathan; Weisz, David; Presser Aiden, Aviva; Aiden, Erez Lieberman; Schermelleh, Lothar; Vannini, Alessandro; Nasmyth, Kim; Center for Theoretical Biological Physics
    Dramatic change in chromosomal DNA morphology between interphase and mitosis is a defining features of the eukaryotic cell cycle. Two types of enzymes, namely cohesin and condensin confer the topology of chromosomal DNA by extruding DNA loops. While condensin normally configures chromosomes exclusively during mitosis, cohesin does so during interphase. The processivity of cohesin’s loop extrusion during interphase is limited by a regulatory factor called WAPL, which induces cohesin to dissociate from chromosomes via a mechanism that requires dissociation of its kleisin from the neck of SMC3. We show here that a related mechanism may be responsible for blocking condensin II from acting during interphase. Cells derived from patients affected by microcephaly caused by mutations in the MCPH1 gene undergo premature chromosome condensation. We show that deletion of Mcph1 in mouse embryonic stem cells unleashes an activity of condensin II that triggers formation of compact chromosomes in G1 and G2 phases, accompanied by enhanced mixing of A and B chromatin compartments, and this occurs even in the absence of CDK1 activity. Crucially, inhibition of condensin II by MCPH1 depends on the binding of a short linear motif within MCPH1 to condensin II’s NCAPG2 subunit. MCPH1’s ability to block condensin II’s association with chromatin is abrogated by the fusion of SMC2 with NCAPH2, hence may work by a mechanism similar to cohesin. Remarkably, in the absence of both WAPL and MCPH1, cohesin and condensin II transform chromosomal DNAs of G2 cells into chromosomes with a solenoidal axis.
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    Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample
    (Elsevier, 2024) Sandoval-Velasco, Marcela; Dudchenko, Olga; Rodríguez, Juan Antonio; Pérez Estrada, Cynthia; Dehasque, Marianne; Fontsere, Claudia; Mak, Sarah S. T.; Khan, Ruqayya; Contessoto, Vinícius G.; Oliveira Junior, Antonio B.; Kalluchi, Achyuth; Zubillaga Herrera, Bernardo J.; Jeong, Jiyun; Roy, Renata P.; Christopher, Ishawnia; Weisz, David; Omer, Arina D.; Batra, Sanjit S.; Shamim, Muhammad S.; Durand, Neva C.; O’Connell, Brendan; Roca, Alfred L.; Plikus, Maksim V.; Kusliy, Mariya A.; Romanenko, Svetlana A.; Lemskaya, Natalya A.; Serdyukova, Natalya A.; Modina, Svetlana A.; Perelman, Polina L.; Kizilova, Elena A.; Baiborodin, Sergei I.; Rubtsov, Nikolai B.; Machol, Gur; Rath, Krisha; Mahajan, Ragini; Kaur, Parwinder; Gnirke, Andreas; Garcia-Treviño, Isabel; Coke, Rob; Flanagan, Joseph P.; Pletch, Kelcie; Ruiz-Herrera, Aurora; Plotnikov, Valerii; Pavlov, Innokentiy S.; Pavlova, Naryya I.; Protopopov, Albert V.; Di Pierro, Michele; Graphodatsky, Alexander S.; Lander, Eric S.; Rowley, M. Jordan; Wolynes, Peter G.; Onuchic, José N.; Dalén, Love; Marti-Renom, Marc A.; Gilbert, M. Thomas P.; Aiden, Erez Lieberman; Center for Theoretical Biological Physics
    Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.