Nuclear Blebbing is Affected by both Lamin Levels and Chromatin State

 Abnormal nuclear morphology is a characteristic of many human diseases such as cancers and heart diseases. Identifying the abnormal shape of a nucleus was an early technique for the diagnosis of cancer, dating back to 1928 with the start of using the pap smear as screening for cervical cancer. It is important to investigate this common phenotype of the disease. Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins (Stephens et. al.) discuss how chromatin state and lamin levels can impact nuclear blebbing. 

 

            The nucleus is ellipsoidal in shape and its structure is provided by chromatin and lamins. Chromatin consists of DNA wrapped around histones and chromatin can be modified in multiple ways to be either in its decompacted state as euchromatin, or in its compact state as heterochromatin. Lamins are located in the periphery of the nucleus, just below the nuclear membrane, and consist of several types. Nuclear blebbing is the herniation of the nucleus, often located on the major axis of a nucleus, and contains high levels of euchromatin as well as low levels of lamin B1. Cells such as MEF and HT1080 cell lines were used in several conditions to impact blebbing. Increasing the levels of euchromatin in the nucleus using a histone deacetylase inhibitor significantly increased blebbing and made the nucleus weaker than the wild type. Blebbing was quantified as percent blebbed in a population, and nucleus strength was quantified by isolating nuclei and obtaining force measurements. Decreasing levels of heterochromatin to achieve higher levels of euchromatin in the nucleus by a histone methyltransferase inhibitor also significantly increased blebbing and weakened the nucleus compared to the wild type. This shows that increasing the levels of decompact chromatin by either increasing the amount of euchromatin or decreasing the amount of heterochromatin can increase blebbing and weaken the nucleus. Lamin levels were adjusted by using cell lines where the genes that express lamin A/C or B1/B2 were silenced so that levels of lamins decrease. For a cell that does not express the Lamin B1 gene, blebbing increases. As a result, this means that both chromatin and lamins play an important role in the structural integrity of the nucleus and both are involved in the cell’s capacity to bleb. 

            

This paper gives a new and different viewpoint on how blebs form because previous reports of bleb formation are on the basis of lamin alterations alone, not changes in chromatin state. Although it has been known that changing lamin levels affects the frequency of blebbing, the modifications in the chromatin state in this paper reveal a new mechanical basis for why blebs form. 

 

Understanding diseases often includes investigating what is going on at the cellular level. Although abnormal nuclear morphology has been used as a tool for a long time as an indicator of the disease, the mechanics of nucleus shape is not yet fully understood. This paper raises many questions about these nuclear blebs and how they relate to complications associated with diseases such as DNA damage and the deregulated cell cycle. 

 

Samantha Bunner (1) 

Sources:

Stephens, AD, Liu PZ, Banigan EJ, Almassaldha LM, Backman V, Adam SA, Goldman RD, Marko JF (2017). Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins. Molecular Biology of the Cell, Volume 29, 220-233 

George A. Vilos, The history of the papanicolaou smear and the Odyssey of George and Andromache Papanicolaou, Obstetrics & Gynecology, Volume 91, Issue 3,1998, Pages 479-483, ISSN 0029-7844, https://doi.org/10.1016/S0029-7844(97)00695-9.

Comments

  1. Haya UsmaniSeptember 28, 2022 at 9:48 AM

    Hi Samantha! Your post was interesting to read since I learned about what blebbing is. It is critical to study the cellular physiology in the body in order to learn about mishaps and diseases that may be caused by several different factors. Its interesting to know how a change in concentration of specific factors can fully cause a change in the downstream processes and lead to diseases. How is blebbing corrected or prevented?

    ReplyDelete
    Replies
    1. AnonymousOctober 1, 2022 at 5:05 PM

      Hi Haya! For blebbing correction, I think increasing levels of heterochromatin, and mitotic events rescue blebs. By increasing levels of the compact heterochromatin, the nuclear rigidity changes. By going through mitosis, the nuclear envelope disassembles and the two daughter nuclei do not have the same bleb from the parent cell. As for prevention, that is an interesting question that I think would be really cool to investigate.

      Delete
    2. AnonymousOctober 1, 2022 at 5:05 PM

      (- Samantha Bunner)

      Delete
  2. Caitlin HooperSeptember 28, 2022 at 10:30 AM

    Hi Samantha! This blog was super interesting as this concept is something I haven't really heard much of before. It is always interesting to hear about new discoveries in science, especially when they almost steer away from what was previously known. How do you think this new breakthrough in information could possibly lead to new cures for diseases including cancer?

    ReplyDelete
  3. Lydia LitvakSeptember 28, 2022 at 11:07 AM

    Hi Samantha! I was never aware of nuclear blebbing before this blog post and found your article to be pretty interesting. As more research is continued regarding this weakening of the nucleus, I wonder what therapies may come about to help cancer patients and other diseases regarding nuclear instability. Also, if lamin levels or heterochromatin levels were targeted to avoid blebbing, what are the potential molecular collateral damages this may induce?

    ReplyDelete
  4. AnonymousSeptember 28, 2022 at 12:00 PM

    This is the first time I've heard of blebbing and I'm curious to know more. Do you think this could help better understand mental illness as well?

    ReplyDelete
    Replies
    1. AlannaSeptember 28, 2022 at 12:01 PM

      Forgot to add my name!

      Delete
    2. AnonymousOctober 1, 2022 at 5:15 PM

      Hi Alanna! When reading this paper, I did not consider a connection to mental illness with nuclear blebbing. I don't know much about mental illness at the cellular level other than epigenetic factors, but it would be very interesting to look further into! I will definitely keep this question in mind as I read about this phenomenon more!
      - Samantha Bunner

      Delete
  5. AnonymousSeptember 28, 2022 at 4:52 PM

    Hi Samantha!
    It was interesting to hear about nuclear blebbing and how increased levels of euchromatin lead to more blebbing and a weakened nucleus. Do you know if increased levels of heterochromatin would result in less blebbing? And, would this have any negative effects on the cell?
    - Tiffany Pham

    ReplyDelete
    Replies
    1. AnonymousOctober 1, 2022 at 4:47 PM

      Hi Tiffany! Yes, increased levels of heterochromatin does 'reverse or suppress' blebbing in the cell. This can be done by adding methyl groups to histones to make them in more compact state. That is a good question as to whether this has any negative effects on the cell. Heterochromatin is the compact state of chromatin, and it can either be facultative or constitutive. Constitutive heterochromatin includes the telomeres and centromeres of chromosomes that are always compact. Facultative heterochromatin is the kind that will be turned on and off as needed such as for transcription. Maybe it depends on what kind of heterochromatin is being increased? That's a great question that would be really cool to investigate.

      Delete
    2. AnonymousOctober 1, 2022 at 5:01 PM

      (the last comment was Samantha Bunner)

      Delete

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