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Loss-of-Function Mutation in a Repressor Module of Human-Specifically Activated Enhancer HACNS1

Sumiyama, K. ; Saitou, N.

Molecular Biology and Evolution, 11/01/2011, Vol.28(11), pp.3005-3007 [Tạp chí có phản biện]

ISSN: 0737-4038 ; E-ISSN: 1537-1719 ; DOI: http://dx.doi.org/10.1093/molbev/msr231

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  • Nhan đề:
    Loss-of-Function Mutation in a Repressor Module of Human-Specifically Activated Enhancer HACNS1
  • Tác giả: Sumiyama, K. ; Saitou, N.
  • Chủ đề: Biology
  • Là 1 phần của: Molecular Biology and Evolution, 11/01/2011, Vol.28(11), pp.3005-3007
  • Mô tả: The cis-regulatory element contributed to gaining humanness is of great interest in human evolutionary studies. A human-accelerated region exceeding neutral evolutionary rates, termed HACNS1, was recently reported as a positively selected sequence acquiring novel TF-binding sites responsible for human-specific gain of limb enhancer function. However, another possibility is loss of function in repressor element in HACNS1. Signature of the human substitutions in the 81-bp region infers that a GC-biased gene conversion (BGC) might create these seemingly excessive substitutions. To evaluate the 81-bp function, we performed transgenic mouse assay of the HACNS1 construct lacking the 81-bp region. The deleted construct showed similar enhancer activity to the intact human HACNS1, suggesting that the function of the human 81-bp region is not an activating enhancer but rather a disrupted repressor. This result infers that loss of function in the HACNS1 81-bp region, possibly via a BGC, played an important role in human-specific evolution.
  • Ngôn ngữ: English
  • Số nhận dạng: ISSN: 0737-4038 ; E-ISSN: 1537-1719 ; DOI: http://dx.doi.org/10.1093/molbev/msr231

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