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Study explores the boundaries of embryonic development

COURTESY OF ELIFE

If all of the DNA in a human cell was stretched out, it would be about two meters long. The nucleus of a human cell, on the other hand, has a diam­e­ter of just 6 microm­e­ters, more than 300,000 times smaller, so the DNA mol­e­cules that carry all the genetic infor­ma­tion in the cell need to be care­fully folded to fit inside the nucleus. Cells meet this chal­lenge by com­bin­ing their DNA mol­e­cules with pro­teins to form a com­pact and highly orga­nized struc­ture called chro­matin. Pack­ag­ing DNA into chro­matin also reduces dam­age to it.

But what hap­pens when the cell needs to express the genes car­ried by the DNA as pro­teins or other gene prod­ucts? The answer is that the com­pact struc­ture of chro­matin relaxes and opens up, which allows the DNA to be tran­scribed into mes­sen­ger RNA. Indeed, pack­ing DNA into chro­matin makes this process more reli­able, thus ensur­ing that the cell only pro­duces pro­teins and other gene prod­ucts when it needs them. How­ever, because cross-talk between neigh­bor­ing genes could poten­tially dis­rupt or change gene expres­sion pat­terns, cells evolved spe­cial ele­ments called bound­aries or insu­la­tors to stop this from hap­pen­ing. These bound­ary fac­tors divide the chro­mo­somes into sub­do­mains that can func­tion inde­pen­dently of each other.

Since the pro­tein fac­tors impli­cated in bound­ary func­tion seemed to be active in all tis­sues and cell types, it was assumed for many years that these bound­aries and the result­ing chro­matin domains were fixed. How­ever, a num­ber of recent stud­ies have shown that bound­ary activ­ity can be sub­ject to reg­u­la­tion, and thus chro­matin domains are dynamic struc­tures that can be defined and rede­fined dur­ing devel­op­ment to alter pat­terns of gene expression.

New research from the lab­o­ra­tory of Paul Schedl at Prince­ton Uni­ver­sity has uncov­ered a new fruit fly bound­ary fac­tor that, unlike pre­vi­ously char­ac­ter­ized fac­tors, is active only dur­ing a spe­cific stage of devel­op­ment. The Elba fac­tor is also unusual in that it is made of three dif­fer­ent pro­teins, known as Elba1, Elba2, and Elba3, and all three must be present for it to bind to DNA. The lead author of the study was Tsu­tomo Aoki of the Prince­ton Uni­ver­sity Depart­ment of Mol­e­c­u­lar Biol­ogy. Aoki worked with co-authors Ali Sarkeshik and John Yates from the Scripps Research Insti­tute in La Jolla, CA.

While Elba2 is present dur­ing most stages of devel­op­ment, the other two Elba pro­teins are only present dur­ing early embry­onic devel­op­ment, so the bound­ary fac­tor is only active in early embryos. In addi­tion to reveal­ing a new mech­a­nism for con­trol­ling bound­ary activ­ity as an organ­ism devel­ops, the stud­ies of Aoki et al. pro­vide fur­ther evi­dence that chro­matin domains can be dynamic.

Aoki, Tsu­tomu, Ali Sarkeshik, John Yang, and Paul Schedl. Elba, a novel devel­op­men­tally reg­u­lated chro­matin bound­ary fac­tor is a hetero-tripartite DNA bind­ing com­plex. eLife 2012;1:e00171
 

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