Molecular Characterization of HOXA2 and HOXA3 Binding Properties.

Molecular Characterization of HOXA2 and HOXA3 Binding Properties.
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DOI:
10.3390/jdb9040055
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发表时间:
2021-12-03
影响因子:
2.7
通讯作者:
Bobola N
Bobola N
中科院分区:
其他
文献类型:
--
作者:
Mallen J;Kalsan M;Zarrineh P;Bridoux L;Ahmad S;Bobola N

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高度保守的HOX同源结构域(HD)转录因子(TF)确定了两侧动物前后轴沿着不同身体部位的身份。片段多样化和不同结构的形态发生是通过产生沿前后轴沿着的HOX表达的精确模式和通过不同HOX TF指导独特和特异性转录程序的能力来实现的。然而,HOX在体外的结合特性,其特征在于识别类似的AT丰富的结合序列,不占不同的HOX的能力,以指导片段特异性转录程序。为了解决这个问题,我们之前比较了HOXA 2和HOXA 3在体内的结合。在这里,我们探讨,如果在体内观察到的序列基序富集在体外结合亲和力的解释。出乎意料的是,我们发现HOXA 2峰中最高富集的基序在体外不被HOXA 2识别,这突出了研究HOX在其生理背景下结合的重要性。我们还报道了HOXA 2和HOXA 3异源二聚化的能力,这可能对体内HOX图案功能具有功能性后果。
The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero–posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero–posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo.
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