4.3 Article

Chromatin remodeling factor CECR2 forms tissue-specific complexes with CCAR2 and LUZP1

Journal

BIOCHEMISTRY AND CELL BIOLOGY
Volume 99, Issue 6, Pages 759-765

Publisher

CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/bcb-2021-0019

Keywords

CECR2; LUZP1; CCAR2; chromatin remodeling factor; neural tube defects

Funding

  1. Natural Sciences and Engineering Research Council (NSERC)
  2. Alberta Queen Elizabeth II Graduate Scholarship
  3. NSERC
  4. Alberta Innovates Technology Futures

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CECR2 is a chromatin remodeling factor crucial for neural tube closure and reproduction. Loss-of-function mutations in Cecr2 primarily result in perinatal lethal neural tube defect exencephaly, with non-penetrant mice showing subfertility. The CECR2-containing remodeling factor (CERF) complex in embryonic stem cells includes SMARCA5, SMARCA1, CCAR2, and LUZP1, with LUZP1 potentially playing a role in stabilizing the complex in ES cells.
Chromatin remodeling complexes alter chromatin structure to control access to DNA and therefore control cellular processes such as transcription, DNA replication, and DNA repair. CECR2 is a chromatin remodeling factor that plays an important role in neural tube closure and reproduction. Loss-of-function mutations in Cecr2 result primarily in perinatal lethal neural tube defect exencephaly, with non-penetrant mice that survive to adulthood exhibiting subfertility. CECR2 forms a complex with ISWI proteins SMARCA5 and (or) SMARCA1; however, further information on the structure and function of the complex is not known. Therefore, we identified candidate components of the CECR2-containing remodeling factor (CERF) complex in embryonic stem (ES) cells using mass spectroscopy. Both SMARCA5 and SMARCA1 were confirmed to be present in the CERF complexes in ES cells and testes. However, the novel proteins CCAR2 and LUZP1 are CERF components in ES cells, but not in the testis. This tissue specificity in mice suggests that these complexes may also have functional differences. Furthermore, LUZP1, the loss of which is also associated with exencephaly, appears to play a role in stabilizing the CERF complex in ES cells.

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