The complete sequences of the galago and rabbit beta-globin locus control regions: extended sequence and functional conservation outside the cores of DNase hypersensitive sites.

The complete sequences of the galago and rabbit beta-globin locus control regions: extended sequence and functional conservation outside the cores of DNase hypersensitive sites.
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夜猴和兔 β 珠蛋白基因座控制区的完整序列:DNA 酶超敏位点核心外的扩展序列和功能保守性。

DOI:
10.1006/geno.1996.4458
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发表时间:
1997
期刊:
Genomics.
影响因子:
--
通讯作者:
Hardison,R
Hardison,R
中科院分区:
--
文献类型:
--
作者:
Slightom,JL;Bock,JH;Tagle,DA;Gumucio,DL;Goodman,M;Stojanovic,N;Jackson,J;Miller,W;Hardison,R

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哺乳动物β-珠蛋白基因的基因座控制区(LCR)在基因簇的5 '端至少覆盖17kb,与染色质结构域的打开、增强和与邻近序列的隔离有关。LCR的功能解剖定义了标记该调控区域的五个主要dna酶敏感位点(HSs)中的四个的最小核心。为了充分研究哺乳动物β-珠蛋白LCR同源物的保守序列模式,我们确定了加拉果β-珠蛋白LCR的完整DNA序列,并完成了兔LCR先前未测序的区域。将这些序列与人类、山羊和小鼠的lcr同时比对,发现了使用三种基本独立的方法检测到的保守序列(系统发育足迹)。最高度保守的片段既存在于核内,也存在于核两侧的一些区域,但不是全部。这些结果证明了良好保守序列的扩展模式,其中许多序列位于最小核心之外,并且我们表明,包括HS3在内的区域打开结构域所需的关键序列映射到最小核心约1 kb 5 '。不同的系统发育足迹,包含在非人类哺乳动物中保守的序列,而不是在人类中,主要是在HS3周围发现的,这与一些物种特异性的功能差异一致,这些差异可能对发育过程中血红蛋白转换的差异很重要。
The locus control region (LCR) of mammalian β-globin genes covers at least 17 kb at the 5′ end of the gene cluster and has been implicated in chromatin domain opening, enhancement, and insulation from neighboring sequences. Functional dissection of the LCR has defined the minimal cores for four of the five major DNase hypersensitive sites (HSs) that mark this regulatory region. To examine fully the patterns of conserved sequences in the mammalian homologs to the β-globin LCR, we determined the complete DNA sequence of the galago β-globin LCR and completed previously unsequenced regions of the rabbit LCR. Simultaneous alignment of these sequences with the human, goat, and mouse LCRs revealed conserved sequences (phylogenetic footprints) detected using three largely independent methods. The most highly conserved segments are found both within the HS cores and in some but not all regions flanking the cores. These results argue for an extended pattern of well-conserved sequences, many of which lie outside the minimal cores, and we show that a key sequence required for domain opening by the region including HS3 maps about 1 kb 5′ to the minimal core. Differential phylogenetic footprints, containing sequences conserved in nonhuman mammals but not in humans, are found primarily around HS3, consistent with some species-specific differences in function that may be important for differences in hemoglobin switching during development.
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