Mutational analysis of human heat-shock transcription factor 1 reveals a regulatory role for oligomerization in DNA-binding specificity.
Mutational analysis of human heat-shock transcription factor 1 reveals a regulatory role for oligomerization in DNA-binding specificity.
复制标题
人类热休克转录因子 1 的突变分析揭示了寡聚化在 DNA 结合特异性中的调节作用。
作者：
Yukiko Takemori;Yasuaki Enoki;N. Yamamoto;Y. Fukai;K. Adachi;H. Sakurai
HSF（热休克转录因子）三聚体结合靶基因的HSE（热休克元件）调控序列，调控基因表达。典型的HSE由至少三个连续的5bp序列nGAAn倒置重复组成。酵母HSF能够识别nGAAn序列阵列中含有间隙的不连续HSEs；然而，hHSF1（人HSF1）在体外、酵母和HeLa细胞中不能识别这些位点。在本研究中，我们分离了表达hhsf1的酵母细胞温度敏感生长缺陷的抑制因子。基因内抑制因子在hHSF1的dna结合域中含有氨基酸取代，使hHSF1能够调节含有不连续HSEs的基因的转录。这些取代促进了hHSF1的寡聚化，表明dna结合结构域对这种构象变化很重要。此外，hHSF1的其他低聚衍生物能够识别不连续的hhs1。这些结果表明，寡聚化的调节对hHSF1的HSE特异性很重要，并暗示hHSF1在不同的细胞过程中具有通过不同类型的hs1结合和调节基因表达的能力。
HSF (heat-shock transcription factor) trimers bind to the HSE (heat-shock element) regulatory sequence of target genes and regulate gene expression. A typical HSE consists of at least three contiguous inverted repeats of the 5-bp sequence nGAAn. Yeast HSF is able to recognize discontinuous HSEs that contain gaps in the array of the nGAAn sequence; however, hHSF1 (human HSF1) fails to recognize such sites in vitro, in yeast and in HeLa cells. In the present study, we isolated suppressors of the temperature-sensitive growth defect of hHSF1-expressing yeast cells. Intragenic suppressors contained amino acid substitutions in the DNA-binding domain of hHSF1 that enabled hHSF1 to regulate the transcription of genes containing discontinuous HSEs. The substitutions facilitated hHSF1 oligomerization, suggesting that the DNA-binding domain is important for this conformational change. Furthermore, other oligomerization-prone derivatives of hHSF1 were capable of recognizing discontinuous HSEs. These results suggest that modulation of oligomerization is important for the HSE specificity of hHSF1 and imply that hHSF1 possesses the ability to bind to and regulate gene expression via various types of HSEs in diverse cellular processes.
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影响因子：
56.9
作者：
HARRISON, CJ;BOHM, AA;NELSON, HCM
通讯作者：
NELSON, HCM
影响因子：
10.5
作者：
Ahn, SG;Liu, PCC;Thiele, DJ
通讯作者：
Thiele, DJ
影响因子：
3.3
作者：
Trinklein, ND;Murray, JI;Myers, RM
通讯作者：
Myers, RM
影响因子：
10.5
作者：
Ahn, SG;Thiele, DJ
通讯作者：
Thiele, DJ